Organ Systems Exam 2! Flashcards
- What is the difference between axons and dendrites?
- What is the difference between axons and dendrites?
Various examples of
neurons
• one axon, but many
dendrites
Neurons
Basic structural features
• Cell body
• Axon
• Dendrites
• Synapse
Nomenclature
PNS CNS
Cell bodies Ganglion Nucleus
Axons Nerve Tract
• Nucleus also sometimes called a body
• Tract also called fasciculus, funiculus,
peduncle, column, lemniscus,
commissure or capsule
- What are Schwann cells and how do they interact with neuronal axons?
- What are Schwann cells and how do they interact with neuronal axons?
Glia
All neurons in the PNS are
surrounded by Glia (Schwann cells)
• Schwann cells:
• PNS glial cell surrounds all peripheral
nerve axons and cell bodies
• Gaps between cells are the nodes of
Ranvier
• Myelinated vs unmyelinated axons (more
of this later)
- What are the three CT layers surrounding a large nerve? What is the basal lamina in nerves? What is its significance in regeneration? 1st Question!
3. What are the three CT layers surrounding a large nerve? What is the basal lamina in nerves? What is its significance in regeneration?
Connective tissue around nerves
Epineurium
Perineurium
• Fascicles
Endoneurium
- What are the three CT layers surrounding a large nerve? What is the basal lamina in nerves? What is its significance in regeneration? 2nd part!
- What are the three CT layers surrounding a large nerve? What is the basal lamina in nerves? What is its significance in regeneration?
Fascicle
• UMF (unmyelinated) and MF
(myelinated) fibers; V vessel; F
fibroblast
Endoneurium within fascicle
• Matrix around glial cells form
endoneurial tubes
Basal Lamina
• secreted by Schwann cells; interface
between Schwann cells and
endoneurium
• contains laminin, promotes growth
and regeneration of axons and glia
- What are nervi nervorum and what do they innervate? What are vasa nervorum and what do they supply? Distinguish between nerve trunk pain and dysesthetic pain.
- What are nervi nervorum and what do they innervate? What are vasa nervorum and what do they supply? Distinguish between nerve trunk pain and dysesthetic pain.
[*] Nervi nervorum: local nerves to CT of nerves
[*] Vasa nervorum: local blood vessels to nerves
Nervi Nervorum
• nerve trunk pain
• dysesthetic pain
>>Nerves to the nerves.
Vasa nervorum
• First degree neuropathic injury due to
temporary compression of
nerves/vessels causes numbness
>>EX: Your arm goes to sleep after leaning against the nerve while sleeping.
Nerve trunk pain: local pain
Dysesthetic pain - when you hit your funny bone and it shoots out to your finger. You’ve created an artificial sense of pain from your finger. It’s called line labeling. If you stimulate a neuron along this length, you’ll notice the same sensation.
- Distinguish the following: dorsal/ventral horn, dorsal/ventral root, dorsal/ventral rami. What structures are located in the dorsal root? What are in the ventral root? I
- Distinguish the following: dorsal/ventral horn, dorsal/ventral root, dorsal/ventral rami. What structures are located in the dorsal root? What are in the ventral root?
- DORSAL ROOT GANGLION
- cluster of cell bodies of sensory neurons
- pseudo-unipolar neuron
- central and peripheral branches
- SYMPATHETIC GANGLIA TRUNK/CHAIN
- perpendicular to peripheral nerves
- postganglionic neuron cell bodies (see below)
- grey and white rami5. Distinguish the following: dorsal/ventral horn, dorsal/ventral root, dorsal/ventral rami. What structures are located in the dorsal root? What are in the ventral root?
Internal structure of spinal cord
Gray matter
• Ventral (Anterior) horn
• Dorsal (Posterior) horn
White matter
• Axons
• Myelin “whitens” the tissue.
PERIPHERAL NERVES
• ROOTLETS converge into the ROOTS
• DORSAL and VENTRAL ROOTS unite to form SPINAL NERVE
• SPINAL NERVE splits into RAMI
• Dorsal ramus innervates deep back muscles and overlying skin
• Ventral ramus innervates remaining muscles, skin, etc.
• PERIPHERAL NERVE = dorsal and ventral rami;
• PNS: nerves outside the brain and spinal cord
- Distinguish the following: dorsal/ventral horn, dorsal/ventral root, dorsal/ventral rami. What structures are located in the dorsal root? What are in the ventral root? II
- Distinguish the following: dorsal/ventral horn, dorsal/ventral root, dorsal/ventral rami. What structures are located in the dorsal root? What are in the ventral root?
- DORSAL ROOT GANGLION
- cluster of cell bodies of sensory neurons
- pseudo-unipolar neuron
- central and peripheral branches
- SYMPATHETIC GANGLIA TRUNK/CHAIN
- perpendicular to peripheral nerves
- postganglionic neuron cell bodies (see below)
- grey and white rami5. Distinguish the following: dorsal/ventral horn, dorsal/ventral root, dorsal/ventral rami. What structures are located in the dorsal root? What are in the ventral root?
Internal structure of spinal cord
Gray matter
• Ventral (Anterior) horn
• Dorsal (Posterior) horn
White matter
• Axons
• Myelin “whitens” the tissue.
PERIPHERAL NERVES
• ROOTLETS converge into the ROOTS
• DORSAL and VENTRAL ROOTS unite to form SPINAL NERVE
• SPINAL NERVE splits into RAMI
• Dorsal ramus innervates deep back muscles and overlying skin
• Ventral ramus innervates remaining muscles, skin, etc.
• PERIPHERAL NERVE = dorsal and ventral rami;
• PNS: nerves outside the brain and spinal cord
- What is the structure of sensory neurons and how do they differ from other neurons?
- What is the structure of sensory neurons and how do they differ from other neurons?
- DORSAL ROOT GANGLION
- cluster of cell bodies of sensory neurons
- pseudo-unipolar neuron
- central and peripheral branches
- SYMPATHETIC GANGLIA TRUNK/CHAIN
- perpendicular to peripheral nerves
- postganglionic neuron cell bodies (see below)
- grey and white rami
Constituents of a Peripheral Nerve
Sensory neurons (blue)
• convey info from periphery to CNS
• enters dorsal root & horn
• cell body in dorsal root ganglion
Motor neurons (red)
• convey info from CNS to skeletal muscle
• Cell body in ventral horn
• Axons exit ventral root
Sympathetic neurons (green)
• found in essentially all nerves
• preganglionic cell body in
intermediolateral column; projects axon
to sympathetic ganglion
• postganglionic cell bodies form the
sympathetic ganglia; project to smooth
muscle/glands, etc
- Distinguish between the dorsal root ganglia and sympathetic ganglia.
- Distinguish between the dorsal root ganglia and sympathetic ganglia.
- DORSAL ROOT GANGLION
- cluster of cell bodies of sensory neurons
- pseudo-unipolar neuron
- central and peripheral branches
- SYMPATHETIC GANGLIA TRUNK/CHAIN
- perpendicular to peripheral nerves
- postganglionic neuron cell bodies (see below)
- grey and white rami
- What are the contents of a typical peripheral nerve? Trace the course of the preganglionic and postganglionic sympathetic neurons.
- What are the contents of a typical peripheral nerve? Trace the course of the preganglionic and postganglionic sympathetic neurons.
Constituents of a Peripheral Nerve
Sensory neurons (blue)
• convey info from periphery to CNS
• enters dorsal root & horn
• cell body in dorsal root ganglion
Motor neurons (red)
• convey info from CNS to skeletal muscle
• Cell body in ventral horn
• Axons exit ventral root
Sympathetic neurons (green)
• found in essentially all nerves
• preganglionic cell body in
intermediolateral column; projects axon
to sympathetic ganglion
• postganglionic cell bodies form the
sympathetic ganglia; project to smooth
muscle/glands, etc
- How do phospholipids organize in the cell membrane? What does the presence of cholesterol have on the cell membrane? What are lipid rafts?
\9. How do phospholipids organize in the cell membrane? What does the presence of cholesterol have on the cell membrane? What are lipid rafts?
Electrical properties of neurons depend
on structural features of the cell membrane
Lipid bilayer
• Phospholipids (4 types) with polar heads and
two hydrophobic hydrocarbon tails
• Spontaneously organize into bilayered sphere
Cholesterol
• Major constituent of
membranes
• Determine permeability to
small water soluble
molecules.
Lipid rafts
• cholesterol & sphingolipids
• parcellate proteins
Permeability of cell membrane
• low permeability to H2O
• high permeability to O2 &
CO2
- How do alpha helical portions of transmembrane proteins relate to the formation of ion channels?
- How do alpha helical portions of transmembrane proteins relate to the formation of ion channels?
Transmembrane proteins
• Alpha helix: part of protein
within lipid membrane
• Multiple crossing: to form
aqueous pores
• Single crossing: to form
receptors for signals
- Describe the equilibrium potential for ions like K and Na. Include: the role of ion flux and concentration gradients & the significance of concentration and electrical gradients. What does it mean to be in equilibrium in this case? What is the sodium-potassium pump and how does it work?
- Describe the equilibrium potential for ions like K and Na. Include: the role of ion flux and concentration gradients & the significance of concentration and electrical gradients. What does it mean to be in equilibrium in this case? What is the sodium-potassium pump and how does it work?
MEMBRANE POTENTIAL
• electrical potential across a cell membrane.
• Membrane potential is produced by
• ion flux
• concentration gradients
ION FLUX
• passage of ions through ion specific, cylindrical, membrane
protein-based ion channels.
• channels lined with negative charges permit passage of
positive, but not negative, ions.
CONCENTRATION GRADIENTS
• produced by Na-K, ATP-ase, the “Na-K Pump”.
• Na-K pump pumps 3 Na ions out &2 K ions in
against their concentration gradients
EQUILIBRIUM POTENTIAL
• membrane polarization created by a single ion.
• Outward flux of K+ down its concentration gradient produces a
negative charge on membrane interior
• The accumulation of negative charge on the interior
electrostatically pulls the K+ inward via an electrical gradient.
• Equilibrium state is reached when outward and inward K+ fluxes
are equal.
• This represents a STEADY STATE type of equilibrium.
Picture: Sodium Potassium pump
- Describe the membrane potential. Include: role of various ions, differences in permeability and concentration gradients, how it differs from the equilibrium potential. What is the dominant ion that determines the membrane potential at rest and why is it so? Why do K+ ions leak out of the cell?
- Describe the membrane potential. Include: role of various ions, differences in permeability and concentration gradients, how it differs from the equilibrium potential. What is the dominant ion that determines the membrane potential at rest and why is it so? Why do K+ ions leak out of the cell?
MEMBRANE POTENTIAL
• electrical potential across a cell membrane.
• Membrane potential is produced by
• ion flux
• concentration gradients
ION FLUX
• passage of ions through ion specific, cylindrical, membrane
protein-based ion channels.
• channels lined with negative charges permit passage of
positive, but not negative, ions.
CONCENTRATION GRADIENTS
• produced by Na-K, ATP-ase, the “Na-K Pump”.
• Na-K pump pumps 3 Na ions out &2 K ions in
against their concentration gradients
EQUILIBRIUM POTENTIAL
• membrane polarization created by a single ion.
• Outward flux of K+ down its concentration gradient produces a
negative charge on membrane interior
• The accumulation of negative charge on the interior
electrostatically pulls the K+ inward via an electrical gradient.
• Equilibrium state is reached when outward and inward K+ fluxes
are equal.
• This represents a STEADY STATE type of equilibrium.
MEMBRANE POTENTIAL, Vm
• Generated by the net flux of all ions.
• Typical membrane polarization from -90 to -55 mV.
• Na-K pump: adds -10mV because of net
outward Na+ pumping: ignore it here.
• Meaning of depolarization and hyperpolarization
GOLDMANN EQUATION quantifies Vm by weighting
each ionic flux with its permeability.
• Balance between motivation (concentration
gradient) and permission (channel permeability)
Ion leakage
• Net outward K+ and inward Na+ drift. Why?
• Recovered by pump
>>>K+ leaks out because there’s not enough potential E to pull it back in! Permeability of Na+ channels are very low. Membrane potential puts a diff. spin on what electrical dynamic of cell is. Sodium pump puts it back into cell happily!
Membrane potential, Vm
• Net driving force = concentration + electrical gradients
• Net flux=net driving force X permeability
K+ net flux is high
Na+ net flux is low (resting conditions)
Picture: Membrane potential
- What are the different types of ion channels and how are they activated? What are non-gated channels? Give an example.
- What are the different types of ion channels and how are they activated? What are non-gated channels? Give an example.
Ion permeability is
determined by gating
properties of channels
TYPE Voltage gated Ligand / Transmitter Mechanically gated
LOCATION Axon hillocks Neural or Skin, retina, etc
Nodes of Ranvier other cell surfaces
STIMULUS De- /Hyper- Neurotransmitters / Pressure, touch, light
Voltage gated ion channels
• Changes permeability in response to
depolarizing or hyperpolarizing charge Non-gated channels
• Normally no change in permeability in response to stimuli
• Up or down regulation can alter number or permeability of channels
• Non-gated K+ channels:
• ubiquitous
• high permeability; “K+ leak channels”
• primary determinant of the resting membrane potential.
- What are receptor potentials and how are they produced? How are they different from action potentials? Ist
- What are receptor potentials and how are they produced? How are they different from action potentials?
Receptor potential
• External stimuli open physically–
gated ion channels in axon terminals
• Receptor potential:
• Graded increase in Na+
permeability
• Ionic current opens voltage-gated
Na+ at the first node of Ranvier,
triggering all-or-none action
potentials
ACTION POTENTIALS
• Graded incoming positive
ionic current depolarizes
membrane to threshold level
of voltage.
• At threshold, rapid
depolarization to positive
value, near E (Na)
• Repolarization to initial
potential
• Hyperpolarization, near E (K)
- What are receptor potentials and how are they produced? How are they different from action potentials?
Receptor potential
• External stimuli open physically–
gated ion channels in axon terminals
• Receptor potential:
• Graded increase in Na+
permeability
• Ionic current opens voltage-gated
Na+ at the first node of Ranvier,
triggering all-or-none action
potentials
ACTION POTENTIALS
• Graded incoming positive
ionic current depolarizes
membrane to threshold level
of voltage.
• At threshold, rapid
depolarization to positive
value, near E (Na)
• Repolarization to initial
potential
• Hyperpolarization, near E (K)
- What are receptor potentials and how are they produced? How are they different from action potentials?
Receptor potential
• External stimuli open physically–
gated ion channels in axon terminals
• Receptor potential:
• Graded increase in Na+
permeability
• Ionic current opens voltage-gated
Na+ at the first node of Ranvier,
triggering all-or-none action
potentials
ACTION POTENTIALS
• Graded incoming positive
ionic current depolarizes
membrane to threshold level
of voltage.
• At threshold, rapid
depolarization to positive
value, near E (Na)
• Repolarization to initial
potential
• Hyperpolarization, near E (K)
Picture: Action potential
Shifts in polarization during the action potential are due to sequential
changes in voltage-gated Na and K channel permeability
A. Rest – both channels closed
B. Depolarization
• Na channel opens in response to depolarization (at threshold)
C. Repolarization
• Na channel spontaneously inactivates
• K channels opens
D. Hyperpolarization
• K channel still open; K flux now through both non-gated & volt-gated
channels
• Potential almost reaches E (K)
- Account for each phase of the action potential in terms of the Na and K channel activities. Why is the initial depolarization and overshoot of the action potential so large in magnitude compared to hyperpolarization?
- Account for each phase of the action potential in terms of the Na and K channel activities. Why is the initial depolarization and overshoot of the action potential so large in magnitude compared to hyperpolarization?
Shifts in polarization during the action potential are due to sequential
changes in voltage-gated Na and K channel permeability
A. Rest – both channels closed
B. Depolarization
• Na channel opens in response to depolarization (at threshold)
C. Repolarization
• Na channel spontaneously inactivates
• K channels opens
D. Hyperpolarization
• K channel still open; K flux now through both non-gated & volt-gated
channels
• Potential almost reaches E (K)
- Describe how raising or lowering the concentration gradient of K can change neuronal excitability. How can alterations in the Na channel affect neuronal excitability.
- Describe how raising or lowering the concentration gradient of K can change neuronal excitability. How can alterations in the Na channel affect neuronal excitability.
Channel population changes in
Na/K channel permeability
• Depolarization: activation of
most Na channels
• Repolarization
• Inactivation of Na
channels
• Slower opening of K
channels
• Hyperpolarization
• Opened K channels that
bring Vm closer to K
equilibrium potential
• Initial depolarization and overshoot of
an action potential is strong, because
Na influx has a high driving force
• Both concentration and electrical
gradients are in the same direction and
summate.
• This is why membrane potential almost
reaches the equilibrium potential for Na
at the peak of the action potential
- Compare myelinated vs unmyelinated axons in terms of: Schwann cell configuration, action potential formation, action potential conduction. What is the difference between absolute and relative refractory periods? Describe the types of ion channels found in nodes of Ranvier and the intermodal regions of the axons.
- Compare myelinated vs unmyelinated axons in terms of: Schwann cell configuration, action potential formation, action potential conduction. What is the difference between absolute and relative refractory periods? Describe the types of ion channels found in nodes of Ranvier and the intermodal regions of the axons.
NEUROPATHY
Neural disease due to damage to either axons or glial cells, or both
Axonal degeneration
• symptoms progress from the hands and feet proximally
Demyelination
• degeneration of glia and the unraveling of myelin sheaths around axons
• Guillain-Barre: demyelination of mostly motor fibers by auto immune response to
infection, surgery, or immunization
• Contrasts with multiple sclerosis (MS), a demyelinating disease in the CNS
Negative symptoms
• loss of sensation, muscle weakness & atrophy
Positive symptoms
• Paresthesia
• Hyperalgesia
Unmyelinated axons Myelinated axons surrounded
surrounded by single by several layers of glial
layer of glial (Schwann) membrane which forms myelin.
Picture: myelinated axons
AP CONDUCTION IN
UNMYELINATED AXONS
• Continuous production of action
potentials along whole axon:
• Limits conduction velocity
• Maintains fidelity
• Voltage-gated Na+ and K+ ion
channels are distributed along the
whole axon
• Ionic current
REFRACTORY PERIOD in unmyelinated axons is
the period of time after an action potential during
which the membrane channels are less responsive
to stimuli
Absolute refractory period
• Na channels inactivated
Relative refractory period
• K channels open
This limits conduction to one direction and a
maximal AP frequency of 500/sec
AP CONDUCTION IN MYELINATED AXONS
• AP’s are only produced in nodes of Ranvier and
the axon hillock; only location of voltage-gated
channels
Axonal myelination increases AP
conduction velocity
• Electrotonic conduction through
internodal areas
• Amplitude of impulses decrease,
because of ionic current leak
• Sufficient depolarizing strength
initiates AP at the next node.
DEMYELINATION
• Common cause of neuropathy, esp. in autoimmune conditions like multiple sclerosis
and Guillain-Barre syndrome
• Glial cells unwind and decrease thickness of myelin, facilitating current leakage
through the membrane
• In demyelinated areas, AP conduction is slowed or halted because excess current
leaks out through non-gated K channels.
• This reduces the available current for the next node of Ranvier, eg.
- What impact does demyelination have on action potential conduction?
- What impact does demyelination have on action potential conduction?
NEUROPATHY
Neural disease due to damage to either axons or glial cells, or both
Axonal degeneration
• symptoms progress from the hands and feet proximally
Demyelination
• degeneration of glia and the unraveling of myelin sheaths around axons
• Guillain-Barre: demyelination of mostly motor fibers by auto immune response to
infection, surgery, or immunization
• Contrasts with multiple sclerosis (MS), a demyelinating disease in the CNS
Negative symptoms
• loss of sensation, muscle weakness & atrophy
Positive symptoms
• Paresthesia
• HyperalgesiaPeripheral Nerve R
DEMYELINATION
• Common cause of neuropathy, esp. in autoimmune conditions like multiple sclerosis
and Guillain-Barre syndrome
• Glial cells unwind and decrease thickness of myelin, facilitating current leakage
through the membrane
• In demyelinated areas, AP conduction is slowed or halted because excess current
leaks out through non-gated K channels.
• This reduces the available current for the next node of Ranvier, eg.
- Compare ionotropic and metabotropic transmission in terms of receptor and postsynaptic actions, duration of effect.
Picture: METABOTROPIC (INDIRECTLY) GATED TRANSMISSION
- Compare ionotropic and metabotropic transmission in terms of receptor and postsynaptic actions, duration of effect.
SYNAPTIC TRANSMISSION
• chemical means by which
neurons communicate with
each other
Transmitter release
• Presynaptic membrane
• Synaptic cleft
• Postsynaptic membrane
IONOTROPIC (DIRECTLY) GATED TRANSMISSION
• Receptors: transmitter / ligand gated ion channels
• neurotransmitter increases permeability to ions, here Na.
METABOTROPIC (INDIRECTLY) GATED TRANSMISSION
• Cell signaling systems that affect postsynaptic enzymes
and/or genomic regulation (“metabolism”)
• Receptors
• Membrane receptors: lipophobic transmitters, eg. adrenergic. (focus of this section)
• Intracellular receptors: lipophilic transmitters, eg. steroid (eg. cortisol) and thyroid hormones
Compare ionotropic and metabotropic systems
• Ionotropic receptor = ion channel; fast onset, shorter duration
• Metabotropic receptor = protein that activates signal transduction; slow onset, longer duration
• Eg. tyrosine kinase, part of a receptor, phosphorylates cytoplasmic proteins
Picture: METABOTROPIC (INDIRECTLY) GATED TRANSMISSION
- Compare ionotropic and metabotropic transmission in terms of receptor and postsynaptic actions, duration of effect.
- Compare ionotropic and metabotropic transmission in terms of receptor and postsynaptic actions, duration of effect. >>Picture: Ionotrophic (Directly) gated transmission
SYNAPTIC TRANSMISSION
• chemical means by which
neurons communicate with
each other
Transmitter release
• Presynaptic membrane
• Synaptic cleft
• Postsynaptic membrane
IONOTROPIC (DIRECTLY) GATED TRANSMISSION
• Receptors: transmitter / ligand gated ion channels
• neurotransmitter increases permeability to ions, here Na.
METABOTROPIC (INDIRECTLY) GATED TRANSMISSION
• Cell signaling systems that affect postsynaptic enzymes
and/or genomic regulation (“metabolism”)
• Receptors
• Membrane receptors: lipophobic transmitters, eg. adrenergic. (focus of this section)
• Intracellular receptors: lipophilic transmitters, eg. steroid (eg. cortisol) and thyroid hormones
Compare ionotropic and metabotropic systems
• Ionotropic receptor = ion channel; fast onset, shorter duration
• Metabotropic receptor = protein that activates signal transduction; slow onset, longer duration
• Eg. tyrosine kinase, part of a receptor, phosphorylates cytoplasmic proteins
- What are EPSPs in terms of transmitter, receptor, postsynaptic action and impact on the initial segment? Do the same for IPSPs.
- What are EPSPs in terms of transmitter, receptor, postsynaptic action and impact on the initial segment? Do the same for IPSPs. Picture: EPSP!
Excitatory Postsynaptic Potentials (EPSP)
• Transient by transmitter-gated Na+/K+ channel
• Na+ influx depolarizes, while K+ exit polarizes,
but net effect is depolarization.
• Excitatory action
• Excitatory synapses (glutamate, eg) usually occur on
dendrites
–
Inhibitory Postsynaptic
Potential (IPSP)
• Transient hyperpolarization by
transmitter-gated Cl- or K+
channel
• Inhibitory action
• Inhibitory synapses (GABA, γ-
aminobutyric acid & glycine)
usually on cell bodies
- What are EPSPs in terms of transmitter, receptor, postsynaptic action and impact on the initial segment? Do the same for IPSPs. Picture: IPSP
- What are EPSPs in terms of transmitter, receptor, postsynaptic action and impact on the initial segment? Do the same for IPSPs. Picture: IPSP
Excitatory Postsynaptic Potentials (EPSP)
• Transient by transmitter-gated Na+/K+ channel
• Na+ influx depolarizes, while K+ exit polarizes,
but net effect is depolarization.
• Excitatory action
• Excitatory synapses (glutamate, eg) usually occur on
dendrites
–
Inhibitory Postsynaptic
Potential (IPSP)
• Transient hyperpolarization by
transmitter-gated Cl- or K+
channel
• Inhibitory action
• Inhibitory synapses (GABA, γ-
aminobutyric acid & glycine)
usually on cell bodies
- What is the significance of summation of EPSPs and IPSPs?
- What is the significance of summation of EPSPs and IPSPs?
Summation of PSP’
s Individual EPSPs cannot elicit APs, so need to summate
• Spatial summation
• Temporal summation
PSP’s adjust MP relative to threshold
• Excitation
• Inhibition
- What does the EEG measure?
- What does the EEG measure?
EEG and neuronal activity
• Thousands of axons synapse upon a
single neuron on dendrites, cell
bodies and, to a lesser degree, axons.
• PSPs summate within a cell
• Synchronization of PSPs among large
populations of neurons produces EEG
waves
- What are G proteins and how do they play a role in the formation of second messengers?
- What are G proteins and how do they play a role in the formation of second messengers?
G PROTEINS
• Complex of α, β, and γ units that utilize GTP (Guanosine triphosphate), hence the name G
• Activated G protein generate cell activity
1. Direct action on the permeability of ion channels
2. Activation of second messengers (eg. cAMP)
3. Gene transcription of proteins
- DIRECT ACTION OF G PROTEINS ON ION CHANNELS
• β, γ portions of G protein directly alter permeability of ion channels
• Eg. In heart deceleration, vagus nerve stimulates the SA node (pacemaker of the heart) using
acetyl choline (Ach) to open K channels and hyperpolarize the cell. This inhibits cardiac action
potentials and decreases the heart rate - ACTIVATION OF SECOND MESSENGERS
• cAMP & cGMP
• IP3/DAG
G protein
↓
Enzyme
↓
2
nd messenger
↓
Effector (kinase or other enzymes)
↓
Cell function
- Compare the effects of ionotropic and metabotropic transmissions on altering ion channel permeability in terms of mechanism and duration of effect.
- Compare the effects of ionotropic and metabotropic transmissions on altering ion channel permeability in terms of mechanism and duration of effect.
Compare ionotropic and metabotropic systems
• Ionotropic receptor = ion channel; fast onset, shorter duration
• Metabotropic receptor = protein that activates signal transduction; slow onset, longer duration
• Eg. tyrosine kinase, part of a receptor, phosphorylates cytoplasmic proteins
Picture: Metabotrophic Transmission
- What is cAMP? What is CREB? Give examples of cAMP actions.
- What is cAMP? What is CREB? Give examples of cAMP actions.
cAMP (cyclic AMP)
• Synthesized from ATP via G protein-adenylate cyclase
• cAMP activates protein kinase A (PKA) via
phosphorylation
• PKA has many functions throughout body
Stimulatory vs inhibitory effects of G proteins
on cAMP
• Different isoforms of alpha portions of G proteins
either stimulate or inhibit cAMP formation.
• total amount of cAMP in cell depends on balance
between the two effects.
SOME ACTIONS OF cAMPVIA PKA
1. cAMP triggers glycogen degradation
to glucose in liver & muscle cells
SOME ACTIONS OF cAMPVIA PKA
1. cAMP triggers glycogen degradation
to glucose in liver & muscle cells
- cAMP releases fatty acids from adipocytes
cAMP stimulates hormone sensitive lipase (HSL) to break down triglycerides into fatty acids
- cAMP alters cell excitability
• Produce long term (hours) changes in
neuronal excitability by altering
permeability of “
non-gated” K+
channels.
- Where does IP3 come from? What generates it? What does IP3 do?
- Where does IP3 come from? What generates it? What does IP3 do?
IP3 /DAG • G protein activates
phospholipase C (PLC), which
cleaves phosphatidyl inositol
(PIP) into second messengers • inositol triphosphate
(IP3) and diacylglycerol
(DAG)
• IP3 releases Ca++ from
endoplasmic reticulum. • Ca regulates smooth
muscle contraction, cell
secretion, etc.
• IP3 is degraded to
inositol and
reincorporated into the
membrane
• DAG (Diacylglycerol) activates
protein kinase C (PKC) • promotes cell division
and proliferation
- What role does cAMP have in long term memory?
- What role does cAMP have in long term memory?
- G PROTEINS REGULATE GENOMIC EXPRESSION
• cAMP-Protein Kinase A (PKA) stimulate CREB (cAMP response
element binding protein).
• CREB: transcription factors that produce long term changes in
nervous system
• Up or down regulation of ion channels, eg. in learning and
memory
• Structure and function of synapses (next slide)
- Give the sequence of events that lead to release of transmitters into the synapse. What role does Ca++ have in this?
- Give the sequence of events that lead to release of transmitters into the synapse. What role does Ca++ have in this?
SYNAPTIC TRANSMISSION
• Signaling factor transmitted across
synapse =
“
nano
” dimensional space
between presynaptic and
postsynaptic membranes
• Presynaptic action potential (AP)
depolarizes membrane
• Presynaptic Ca++ influx through
voltage-gated channels translocates
vesicles
• Amplitude of AP determines amount
of transmitter released.
Neurotransmitters used in the PNS
Synapses are defined by their transmitters and receptors
• Action of a neurotransmitter is determined by its receptors.
• Some non-specificity of transmitters on various receptors
Cholinergic nicotinic and muscarinic synapses
• Acetyl choline (Ach) stimulates nicotinic and muscarinic
receptors
• Synapses
• Nicotinic - on neurons and skeletal muscle
• Muscarinic – body tissues and CNS neurons
Adrenergic synapses
• Catecholamines: norepinephrine, epinephrine and
dopamine
• Norepinephrine, epinephrine stimulate adrenergic
receptors
• Dopamine has its own dopamine receptor
- Compare nicotinic and muscarinic cholinergic receptors in terms of location in the PNS, action and duration of effect.
- Compare nicotinic and muscarinic cholinergic receptors in terms of location in the PNS, action and duration of effect.
Both nicotinic and muscarinic receptors are receptors for acetylcholine. The important difference between the two is their mode of action. Nicotinc acetylcholine receptors (nAChRs) are ionotropic receptors, meaning that they allow ions to pass through them when they bind to acetylcholine. Therefore, these receptors help depolarize the cell in response to acetylcholine and are excitatory.
Muscarinic acetylcholine receptors (mAChRs), on the other hand are metabotropic receptors (G-protein coupled receptors). This means that mAChRs activate G-proteins in response to acetylcholine and these G-proteins can have different cellular responses depending on which G-proteins are activated and on what proteins these G-proteins act.
===
Neurotransmitters used in the PNS Synapses are defined by their transmitters and receptors
• Action of a neurotransmitter is determined by its receptors. • Some non-specificity of transmitters on various receptors
Cholinergic nicotinic and muscarinic synapses • Acetyl choline (Ach) stimulates nicotinic and muscarinic
receptors • Synapses
• Nicotinic - on neurons and skeletal muscle • Muscarinic – body tissues and CNS neurons
Adrenergic synapses • Catecholamines: norepinephrine, epinephrine and
dopamine • Norepinephrine, epinephrine stimulate adrenergic
receptors • Dopamine has its own dopamine receptor
- What is the sequence of catecholamine synthesis from tyrosine? What is the difference between neurons that use norepinephrine as transmitter versus those that use epinephrine?
- What is the sequence of catecholamine synthesis from tyrosine? What is the difference between neurons that use norepinephrine as transmitter versus those that use epinephrine?
NOREPINEPHRINE,
EPINEPHRINE
• Synthetic steps from
tyrosine: Tyrosine, L
-DOPA,
Dopamine, Norepinephrine,
Epinephrine
• Enzymes determine neuron
type
• Reuptake or destruction by
monoamine oxidase (MAO)
or catechol
-
O
-methyl
transferase (COMT
)
- How do neuropeptides compare to cholinergic and adrenergic transmitters in terms of: location of synthesis and vesiculation, postsynaptic action and duration of effects.
- How do neuropeptides compare to cholinergic and adrenergic transmitters in terms of: location of synthesis and vesiculation, postsynaptic action and duration of effects.
Neuropeptides
• Effects: long term changes in ion channel permeability,
number of receptors, gene transcription of proteins, etc
• Synthesis in cell body
• Axonal transport of pre-peptides in vesicles along
microtubules (contrast with other transmitters).
• modified by transported enzymes in the axon terminal
• Co-release with other transmitters; peptides released
Adrenergic receptors (metabotropic)
• Alpha (α1)receptors (IP3 and DAG) regulate Ca++ &
K+ channels.
• Beta (β1, β2) receptors (cAMP) regulate smooth
muscles, metabolism, heart, etc
• Drug actions on beta receptors
• Propranolol blocks receptors, eg decrease HR
• Ephedra (Ma Huang in Chinese) stimulates
epinephrine receptors
• Cocaine or amphetamine inhibit NE reuptake,
prolonging action
at lower thresholds
• Slow destruction by enzymes
• Metabotropic receptors
Neurotransmitters used in the PNS
Synapses are defined by their transmitters and receptors
• Action of a neurotransmitter is determined by its receptors.
• Some non-specificity of transmitters on various receptors
Cholinergic nicotinic and muscarinic synapses
• Acetyl choline (Ach) stimulates nicotinic and muscarinic
receptors
• Synapses
• Nicotinic - on neurons and skeletal muscle
• Muscarinic – body tissues and CNS neurons
Adrenergic synapses
• Catecholamines: norepinephrine, epinephrine and
dopamine
• Norepinephrine, epinephrine stimulate adrenergic
receptors
• Dopamine has its own dopamine receptor
- Describe the neural hierarchy of the ANS starting from the limbic system to the target structures of the autonomic nerves. What are the specific locations of the preganglionic and postganglionic neuron cell bodies of the two parts of the autonomic nervous system?
- Describe the neural hierarchy of the ANS starting from the limbic system to the target structures of the autonomic nerves. What are the specific locations of the preganglionic and postganglionic neuron cell bodies of the two parts of the autonomic nervous system?
PERIPHERAL NERVOUS SYSTEM (PNS)
SOMATIC MOTOR SYSTEM
• Single α-motor neuron in ventral horn
projects to skeletal muscle
AUTONOMIC NERVOUS SYSTEM (ANS)
• Two-neuron in both sympathetic and
parasympathetic nervous systems
• Preganglionic neurons project to
neurons
• Postganglionic neurons project to
tissues: smooth muscle, cardiac
muscle, & glands, etc
AUTONOMIC NERVOUS SYSTEM (ANS)
Sympathetic
• “fight, fright or flight“ (?)
• Preganglionics in T1-L2
• Postganglionic cell bodies in ganglia or
adrenal medulla
• Projections of postganglionic neurons:
internal organs plus peripheral areas, eg. skin
• Increases HR and BP, bronchodilates, etc.
Parasympathetic
• “rest and digest“ (?)
• Preganglionic neurons: long
axons
• Cranial cells in brain stem;
projections
• Sacral cells in S2,3,4 spinal
cord; projections
• Ganglia near or within the target
structures
• Postganglionic neurons: short
axons
• Lowers HR , promote GI
peristalsis, etc
• HYPOTHALAMUS at base of brain controls
the ANS through brain stem structures
• Hypothalamic and brain stem control of the
ANS is governed primarily by the limbic
system which includes areas such as the
hippocampus, cingulate gyrus, amygdala
• Brains stem has centers that govern
all the visceral systems of the body,
especially, cardiovascular,
respiratory, GI
- Compare how motor neurons and postganglionic sympathetic neurons innervate their target tissues.
- Compare how motor neurons and postganglionic sympathetic neurons innervate their target tissues.
PERIPHERAL NERVOUS SYSTEM (PNS)
SOMATIC MOTOR SYSTEM
• Single α-motor neuron in ventral horn
projects to skeletal muscle
AUTONOMIC NERVOUS SYSTEM (ANS)
• Two-neuron in both sympathetic and
parasympathetic nervous systems
• Preganglionic neurons project to
neurons
• Postganglionic neurons project to
tissues: smooth muscle, cardiac
muscle, & glands, etc
>>Picture:
AUTONOMIC NERVOUS SYSTEM (ANS)
Sympathetic
- “fight, fright or flight“ (?)
- Preganglionics in T1-L2
- Postganglionic cell bodies in ganglia or adrenal medulla
- Projections of postganglionic neurons: internal organs plus peripheral areas, eg. skin
- Increases HR and BP, bronchodilates, etc.
Parasympathetic
• “rest and digest“ (?)
• Preganglionic neurons: long
axons
• Cranial cells in brain stem;
projections
• Sacral cells in S2,3,4 spinal
cord; projections
• Ganglia near or within the target
structures
• Postganglionic neurons: short
axons
• Lowers HR , promote GI
peristalsis, etc
Summary of ANS neurotransmitters – Know this!
Summary of ANS neurotransmitters
Learn this!!
Use this and the next slides to understand how
nicotinic, muscarinic and adrenergic
stimulators and inhibitors affect the ANS and
its actions
- If a medicine inhibited acetylcholine esterase, what impact would there be on the innervation of muscle and the activity of sympathetic and parasympathetic systems?
- If a medicine inhibited acetylcholine esterase, what impact would there be on the innervation of muscle and the activity of sympathetic and parasympathetic systems?
Effects[edit]
Potential side effects ofacetylcholinesterase inhibitors[10][11]
mild – usually goes away potentially serious
Diarrhea
Headache
Insomnia
Nausea
Vomiting
Abdominal pain
Lack of appetite
Yellowed skin
Dizziness
Slow heartbeat
Sudden or substantial weight loss
Weakness
Some major effects of cholinesterase inhibitors:
Actions on the parasympathetic nervous system, (the parasympathetic branch of theautonomic nervous system) may cause bradycardia, hypotension, hypersecretion,bronchoconstriction, GI tract hypermotility, and decrease intraocular pressure.
SLUDGE syndrome.
Actions on the neuromuscular junction will result in prolonged muscle contraction.
Administration of reversible cholinoesterase inhibitors is contraindicated with those that have urinary retention due to obstruction.
An acetylcholinesterase inhibitor (often abbreviated AChEI) or anti-cholinesterase is a chemicalthat inhibits the acetylcholinesterase enzyme from breaking down acetylcholine, thereby increasing both the level and duration of action of the neurotransmitter acetylcholine. Reversible, quasi-irreversible (or pseudirreversible in some sources) and irreversible inhibitors exist.[1]
Nicotinic receptors
• Ionotropic : Na /K channels, fast response
• Located in
• Autonomic ganglion; on postganglionic neurons
• Skeletal muscle
• Physostigmine, reversible acetylcholinesterase inhibitor, used for myasthenia gravis. Action?
• Stimulated by nicotine: nicotine is named after the tobacco plant Nicotiana tabacum, which in turn is named after the
French ambassador in Portugal, Jean Nicot de Villemain, who sent tobacco and seeds to Paris in 1560,and who promoted
their medicinal use -Wikipedia
- How are typical muscles packaged in CT? How do nerves and blood vessels approach muscle cells?
- How are typical muscles packaged in CT? How do nerves and blood vessels approach muscle cells?
SKELETAL MUSCLE
CT Medium for nerves and blood vessels
• Epimysium
• Perimysium
• Endomysium
MUSCLE FIBERS are single cells
•
Multiple nuclei, organelles and contractile structures.
• • •
Myogenic cells in somites generate myoblasts and satellite cells Fusion of myoblasts Satellite cells: are stem cells that survive into adulthood. Prenatally, they divide and fuse with the muscle fiber to ensure adequate number of nuclei. Postnatally, they can replace damaged muscle fibers
Sarcolemma: cell membrane
• • T-tubules • Sarcoplasmic Reticulum (equivalent to endoplasmic reticulum) stores and releases Ca++
- What are muscle “fibers”? What are satellite cells and how do they function?
- What are muscle “fibers”? What are satellite cells and how do they function?
MUSCLE FIBERS are single cells
•
Multiple nuclei, organelles and contractile structures.
• • •
Myogenic cells in somites generate myoblasts and satellite cells
Fusion of myoblasts
Satellite cells: are stem cells that survive into adulthood. Prenatally, they divide and fuse with the muscle fiber to ensure adequate number of nuclei. Postnatally, they can replace damaged muscle fibers
Sarcolemma: cell membrane
• • T-tubules • Sarcoplasmic Reticulum (equivalent to endoplasmic reticulum) stores and releases Ca++
- What are muscle “fibers”? What are satellite cells and how do they function? II
- What are muscle “fibers”? What are satellite cells and how do they function?
MUSCLE FIBERS are single cells
•
Multiple nuclei, organelles and contractile structures.
• • •
Myogenic cells in somites generate myoblasts and satellite cells
Fusion of myoblasts
Satellite cells: are stem cells that survive into adulthood. Prenatally, they divide and fuse with the muscle fiber to ensure adequate number of nuclei. Postnatally, they can replace damaged muscle fibers
Sarcolemma: cell membrane
• • T-tubules • Sarcoplasmic Reticulum (equivalent to endoplasmic reticulum) stores and releases Ca++
- What is the sarcoplasmic reticulum and what does it contain? Describe its relationship to the sarcolemma and t-tubules. What is a triad?
- What is the sarcoplasmic reticulum and what does it contain? Describe its relationship to the sarcolemma and t-tubules. What is a triad?
MUSCLE FIBERS are single cells
•
Multiple nuclei, organelles and contractile structures.
• • •
Myogenic cells in somites generate myoblasts and satellite cells Fusion of myoblasts Satellite cells: are stem cells that survive into adulthood. Prenatally, they divide and fuse with the muscle fiber to ensure adequate number of nuclei. Postnatally, they can replace damaged muscle fibers
• • T-tubules • Sarcoplasmic Reticulum (equivalent to endoplasmic reticulum) stores and releases Ca++
SARCOPLASMIC RETICULUM 1. Sarcotubules: Ca++ bound to calsequestrin.
- Terminal cisternae: form triads with t-tubule
>>>>Calcium sequestered back into reticulum through the SR Sarcotubules
MYOFIBRILS & SARCOMERES Myofibrils
• Chain of fused sarcomeres extending the length of muscle fiber
Sarcomere
- Thick and thin myofilaments, including actin and myosin
- Z-lines • Surrounded by SR
- Describe the difference between myofibrils, sarcomeres and myofilaments.
- Describe the difference between myofibrils, sarcomeres and myofilaments.
Myofilaments are the filaments (long chain of proteins) of myofibrils constructed from proteins.[1] The principal types of muscle are striated muscle, obliquely striated muscle and smooth muscle. Various arrangements of myofilaments create different muscles. Striated muscle has transverse bands of filaments. In obliquely striated muscle, the filaments are staggered. Smooth muscle has irregular arrangements of filaments.
Types of myofilaments[edit]
There are three different types of myofilaments: thick, thin, and elastic filaments.
Thick filaments consist primarily of the protein myosin. Each thick filament is approximately 15 nm in diameter, and each is made of several hundred molecules of myosin.
Thin filaments, 7 nm in diameter, consist primarily of the protein actin. All thin filaments are attached to the Z disc.
Elastic filaments, 1 nm in diameter, are made of titin, a large springy protein. They flank each thick filament and anchor it to the Z disc, the end point of a sarcomere.
MYOFIBRILS & SARCOMERES Myofibrils
• Chain of fused sarcomeres extending the length of muscle fiber
Sarcomere
- Thick and thin myofilaments, including actin and myosin
- Z-lines • Surrounded by SR
Sarcomere cytoskeleton
• •
Z-lines connect sarcomeres: “Striated”
Titins (= connectin)
- maintain alignment of myofibrils
- elastic component in muscle
- 15% of the total protein in the myofibril.
Myofilaments
Thin filaments
•
• •
Actin: globular proteins (G actin) polymerized into doubled strands (F actin)
Tropomyosin: on myosin binding sites Troponin: activated by Ca++
Thick filaments
• Myosin • Tails: thick portion • Head and neck: cross bridges
- Describe the underlying structure of a sarcomere in terms of proteins (actin, myosin etc) and cytoskeleton. What is meant by “striated” muscle?
- Describe the underlying structure of a sarcomere in terms of proteins (actin, myosin etc) and cytoskeleton. What is meant by “striated” muscle?
MYOFIBRILS & SARCOMERES Myofibrils
• Chain of fused sarcomeres extending the length of muscle fiber
Sarcomere
- Thick and thin myofilaments, including actin and myosin
- Z-lines • Surrounded by SR
Sarcomere cytoskeleton
• •
Z-lines connect sarcomeres: “Striated”
Titins (= connectin)
- maintain alignment of myofibrils
- elastic component in muscle
- 15% of the total protein in the myofibril.
Striated - has repeating sarcomeres.
- Describe the main features of myosin and actin. How do they bind together?
- Describe the main features of myosin and actin. How do they bind together?
Sarcomere contraction
- Crossbridge actions bring actins (& Z lines) closer together alongside myosin, shortening the sarcomere
- Requires some overlap between actin and myosin.
- Contraction positions can range from overextended (bottom) to severe overlapping of actin fibrils (top)
- Describe the main features of the neuromuscular junction and how it differs from a typical neuron-neuron synapse. How does changing the activity of acetylcholine esterase affect NMJ function?
- Describe the main features of the neuromuscular junction and how it differs from a typical neuron-neuron synapse. How does changing the activity of acetylcholine esterase affect NMJ function?
NEUROMUSCULAR JUNCTION (NMJ)
- Motor neuron axons branch and synapse onto muscle end-plates; last step on conduction map
- Post junctional folds with ACh receptors & acetylcholinesterase
NMJ presynaptic events
•
Ca++ entry into axon terminal promotes exocytosis
- Uncouples vesicle from synapsin and actin, permitting translocation
- Activate SNARES that bind synaptic vesicle to presynaptic membrane for release
NMJ ionotropic transmission End-plate potential, EPP • ACh opens ionotropic nicotinic receptor • Na+/ K+ channel creates EPP, a suprathreshold
depolarization
Muscle action potential • EPP’s depolarizes voltage-gated Na+ channels that
generate muscle action potentials.
One axonal action potential initiates muscle action potential and twitch
Acetylcholinesterase
• • •
In post junctional folds of skeletal cell membrane
Breaks ACh down to choline and acetate
Choline reabsorbed, recycled into vesicles & combined with acetyl CoA
- What is an EPP and how is it different from the muscle action potential? What types of ion channels are involved in each?
- What is an EPP and how is it different from the muscle action potential? What types of ion channels are involved in each?
NMJ ionotropic transmission End-plate potential, EPP • ACh opens ionotropic nicotinic receptor • Na+/ K+ channel creates EPP, a suprathreshold
depolarization
Muscle action potential • EPP’s depolarizes voltage-gated Na+ channels that
generate muscle action potentials.
One axonal action potential initiates muscle action potential and twitch
Editing Needed: 9. Describe how the muscle action potential approaches the triads and what happens when it activates the L-type Ca channel. How is the SR signaled to release Ca++? How does the SR process Ca?
- Describe how the muscle action potential approaches the triads and what happens when it activates the L-type Ca channel. How is the SR signaled to release Ca++? How does the SR process Ca?
Muscle excitation AP leads to Ca++ release from SR
- AP spreads along T-tubule
- AP current activates dihydropyridine receptors (DHP)
- DHP: L type voltage-gated Ca++ channel that does not permit Ca++ flux into cell. Instead it conducts voltage to the physically attached RyR.
- DHP does permit entry of Ca++ in cardiac cells; see heart lecture
- Ryanodine receptor (RyR): Ca++ channel that releases Ca++ from the SR terminal cisternae
MUSCLE FIBERS are single cells
•
Multiple nuclei, organelles and contractile structures.
• • •
Myogenic cells in somites generate myoblasts and satellite cells Fusion of myoblasts Satellite cells: are stem cells that survive into adulthood. Prenatally, they divide and fuse with the muscle fiber to ensure adequate number of nuclei. Postnatally, they can replace damaged muscle fibers
• • T-tubules • Sarcoplasmic Reticulum (equivalent to endoplasmic reticulum) stores and releases Ca++
Sarcolemma: cell membrane
SARCOPLASMIC RETICULUM 1. Sarcotubules: Ca++ bound to calsequestrin. 2. Terminal cisternae: form triads with t-tubule
- What are the roles of Ca and ATP in actin and myosin contraction and relaxation? How does the myosin change during sarcomere contraction?
- What are the roles of Ca and ATP in actin and myosin contraction and relaxation? How does the myosin change during sarcomere contraction?
Sliding filament mechanism of contraction: 4 stages
- Crossbridge attachment 2. Working stroke 3. Detachment 4. ATP hydrolysis
• What conditions are required for actin to bind to myosin?
ADP & Phosphate
• What event triggers bending of the myosin head ?
Release of ADP & Phosphate triggers bending of the myosin head
• What conditions are necessary for muscle to relax? What is meant by rigor?
Adding ATP is necessary for the muscle to relax
• What causes the myosin head to restore its initial position?
ATP Hydrolysis (to ADP & Phosphate)
Temporal summation of twitches
- Increased frequency of AP’ causes summation of contractions to greater forces
- AP’s and Ca++ releases are briefer than twitches, so contraction can repeat before the muscle has relaxed
- Summation can reach a sustained or tetanic contraction (tetanus) where motor unit has been maximally stimulated by its motor neuron
Note relationship between Ca++ influxes and twitch force/duration • Ca++ that generates twitch is rapidly pumped back into the SR • During twitch summation, there is diminished time for Ca++ pumping and muscle
relaxation; can reach tetanic contraction
MECHANICS OF MUSCLE CONTRACTION
Contraction of muscle groups result from temporal and spatial summation of single contractions (twitches) among motor units
Twitch
•
Twitch is a movement of a single motor unit caused by a single action potential
- Duration determined by level of myoplasmic Ca++
- Note time course of AP, myoplasmic Ca++ levels, and twitch force
Sarcomere contraction
- Crossbridge actions bring actins (& Z lines) closer together alongside myosin, shortening the sarcomere
- Requires some overlap between actin and myosin.
- Contraction positions can range from overextended (bottom) to severe overlapping of actin fibrils (top)
How does the myosin change during sarcomere contraction?
- What are the roles of Ca and ATP in actin and myosin contraction and relaxation? How does the myosin change during sarcomere contraction?
Sliding filament mechanism of contraction: 4 stages
- Crossbridge attachment 2. Working stroke 3. Detachment 4. ATP hydrolysis
• What conditions are required for actin to bind to myosin?
ADP & Phosphate
• What event triggers bending of the myosin head ?
Release of ADP & Phosphate triggers bending of the myosin head
• What conditions are necessary for muscle to relax? What is meant by rigor?
Adding ATP is necessary for the muscle to relax
• What causes the myosin head to restore its initial position?
ATP Hydrolysis (to ADP & Phosphate)
Temporal summation of twitches
- Increased frequency of AP’ causes summation of contractions to greater forces
- AP’s and Ca++ releases are briefer than twitches, so contraction can repeat before the muscle has relaxed
- Summation can reach a sustained or tetanic contraction (tetanus) where motor unit has been maximally stimulated by its motor neuron
Note relationship between Ca++ influxes and twitch force/duration • Ca++ that generates twitch is rapidly pumped back into the SR • During twitch summation, there is diminished time for Ca++ pumping and muscle
relaxation; can reach tetanic contraction
MECHANICS OF MUSCLE CONTRACTION
Contraction of muscle groups result from temporal and spatial summation of single contractions (twitches) among motor units
Twitch
•
Twitch is a movement of a single motor unit caused by a single action potential
- Duration determined by level of myoplasmic Ca++
- Note time course of AP, myoplasmic Ca++ levels, and twitch force
Sarcomere contraction
- Crossbridge actions bring actins (& Z lines) closer together alongside myosin, shortening the sarcomere
- Requires some overlap between actin and myosin.
- Contraction positions can range from overextended (bottom) to severe overlapping of actin fibrils (top)
- What is the length-tension relationship of muscle? What two factors alter the force of contraction?
- What is the length-tension relationship of muscle? What two factors alter the force of contraction?
Isometric contraction • Tetanic contraction against a weight that exceeds the maximal force of the muscle • Depends on sarcomere status Length-tension relationship Total muscle tension is the sum of active and passive tensions. • Passive tension: resistance of muscle CT (elastic titin fibers) • Active tension (isometric): proportional to number of cross bridges (maximum at Lo ) • Stretching muscle from contracted state to Lo improves contractility, because of:
- Optimal overlap between actin and myosin
- Increased Ca++ binding affinity to troponin. Beyond the optimal length, Ca++ binding diminishes. With over contraction and actin overlap, stretching readjusts myofibrils to optimal overlap for maximal contraction force
- What is the velocity-tension relationship and hop does it differ from length-tension relationship?
- What is the velocity-tension relationship and hop does it differ from length-tension relationship?
Isotonic contraction • Muscle shortens with constant force exceeding the weight of the mass • Contraction velocity differs depending on actin-myosin crossbridge cycling Velocity-tension relationship • The velocity of isotonic muscle contraction decreases with increased loads • Increased load slows the rate of cross bridge cycling
Isometric contraction • Tetanic contraction against a weight that exceeds the maximal force of the muscle • Depends on sarcomere status Length-tension relationship Total muscle tension is the sum of active and passive tensions. • Passive tension: resistance of muscle CT (elastic titin fibers) • Active tension (isometric): proportional to number of cross bridges (maximum at Lo ) • Stretching muscle from contracted state to Lo improves contractility, because of:
- Optimal overlap between actin and myosin
- Increased Ca++ binding affinity to troponin. Beyond the optimal length, Ca++ binding diminishes. With over contraction and actin overlap, stretching readjusts myofibrils to optimal overlap for maximal contraction force
- What is the difference between twitch, spasm and tetanus?
- What is the difference between twitch, spasm and tetanus?
MECHANICS OF MUSCLE CONTRACTION
Contraction of muscle groups result from temporal and spatial summation of single contractions (twitches) among motor units
Twitch
•
Twitch is a movement of a single motor unit caused by a single action potential
- Duration determined by level of myoplasmic Ca++
- Note time course of AP, myoplasmic Ca++ levels, and twitch force
–
Tetanus • Muscular rigidity and spasms of tetanus are caused by
tetanus toxin (tetanospasmin), which is produced by Clostridium tetani, an anaerobic bacillus
- Rigidity = tonic, involuntary contraction of muscles • Spasms = shorter lasting muscle contractions
- Symptoms: trismus/lockjaw, risus sardonicus (sardonic grin), dysphagia, neck stiffness, abdominal rigidity, and opistotonus, i.e.,hyperactivity of muscles of the head, neck, and trunk
- Differentiate between type I and type II muscle fibers in terms of: myosin type & ATP-ase activity, ATP sources and functional role.
- Differentiate between type I and type II muscle fibers in terms of: myosin type & ATP-ase activity, ATP sources and functional role.
- How do myasthenia gravis, tetanus and their remedies affect neuro- and muscle physiology? How does Botox work?
- How do myasthenia gravis, tetanus and their remedies affect neuro- and muscle physiology? How does Botox work?
Tetanus • Muscular rigidity and spasms of tetanus are caused by
tetanus toxin (tetanospasmin), which is produced by Clostridium tetani, an anaerobic bacillus
- Rigidity = tonic, involuntary contraction of muscles • Spasms = shorter lasting muscle contractions
- Symptoms: trismus/lockjaw, risus sardonicus (sardonic grin), dysphagia, neck stiffness, abdominal rigidity, and opistotonus, i.e.,hyperactivity of muscles of the head, neck, and trunk
Botox (botulinum neurotoxin) enters cell and interferes with SNARE proteins to block Ach release
- What is the sequence of catecholamine synthesis from tyrosine? What is the difference between neurons that use norepinephrine as transmitter versus those that use epinephrine?
- What is the sequence of catecholamine synthesis from tyrosine? What is the difference between neurons that use norepinephrine as transmitter versus those that use epinephrine?
NOREPINEPHRINE,
EPINEPHRINE
• Synthetic steps from
tyrosine: Tyrosine, L
-DOPA,
Dopamine, Norepinephrine,
Epinephrine
• Enzymes determine neuron
type
• Reuptake or destruction by
monoamine oxidase (MAO)
or catechol
-
O
-methyl
transferase (COMT)
