Nervous System Flashcards
Membrane Potential
the electrical disequilibrium that exists between the ECF and ICF is called membrane potential difference or membrane potential (Vm)
Equilibrium Potential
For any given concentration gradient of a single ion, the membrane potential that exactly opposes the concentration gradient is known as the equilibrium potential
What impacts resting membrane potential the most?
The Potassium + Channel.
Making a negative intracellular charge
Two Factors that incfuence a cells membrane potential?
the permeability of the membrane to those ions
the co contraption gradients of different ions across a membrane ( Na+, K+ and Ca2+
Depolarization
If the membrane potential becomes less negative than the resting potential
Hyperpolarization
if the membrane potential becomes more negative, the cell hyperpolarizes
Afferent
Carry information towards CNS
Efferent
Cary information away from CNS
CNS
brain
spinal cord
Peripheral Nervous System (PNS)
Nerve tissue outside the CNS: Cranial nerves and branches, spinal nerves and branches, ganglia, plexuses and sensory receptors
Afferent division
Somatic sensory
Visceral Sensory
Special sensory
Efferent division
Somatic motor
Autonomic motor
A cell body (soma)
considered the control center, with processes that extend outward; dendrites and axons
Dendrites
Receive incoming signals from neighbouring cells
Axons
carry outgoing signals from the integration centre to target cells
Presynaptic terminals
contains transmitting elements
Pseudounipolar
Neurons have a single process called the axon. During development, the dendrite fused with the axon
Bipolar
Bipolar neurons have two relatively equal fibres extending off the central cell body
Anaxonic
Multipolar CNS interneurons are highly branched but lack long extensions
Multipolar
A typical multipolar efferent neutron has 5-7 dendrites, each branching four to six times. A single long axon may branch several times and end at enlarged axon terminals
Afferent
Sensory
Carry information about temperature, pressure, light and other stimuli to the CNS
Interneurons
Complex branching neurons that fascilitate communication between neurons
Efferent
Motor and Autonomic
Motor Efferent
control skeletal muscles
Autonomic Efferent
Influences many internal organs
Sympathetic and parasympathetic
Usually have axon terminals or varicosities
Axonal Transport
The axon is specialized to convey chemical and electrical signals that require a variety of different types of proteins
The axon contains many types of fibres and filaments but lacks ribosomes and ER necessary for protein production, therefore proteins must be produced un the cell body and transported down the axon
Fast Axonal Transport
Membrane bound proteins and organelles (vesicles or mitochondria)
Anterograde: Cell body to axon terminal, up to 400mm/day
Retrograde: Axon terminal to cell body, 200mm/day
Slow Axonal Transport
Cytoplasmic proteins (enzymes) and cytoskeleton proteins
Anterograde, up to 8mm/day some evidence for retro
Not well characterized, may be slower due to frequent periods of pausing of movements
Kinesins
Anterograde transport
Dyneins
Retrograde transport
Synapses
Majority are chemical synapses
Space contains extracellular matrix (proteins and carbohydrates) that hold pre and post synaptic cells in close proximity
Myelin forming Glia
A substance composed of multiple concentric of multiple concentric layers of phospholipid membrane wrapped around an axon
Provides structural stability, acts an insulation around the axon to speed up electrical signals (saltatory conduction), supply trophic factors
Multiple Sclerosis
Disorder resulting from demolition in brain and spinal cord
MS symtoms
Sensory, motor and cognitive issues
Satellite Glial cells
Exist within ganglia (bundle of cell bodies) in the PNS
Form a supportive capsule around the cell bodies for neurons (sensory and autonomic)
Supply nutrients
Structural support, provide a protective cushion
Astrocytes
Highly branched glial cells in CNS believes to make up half of all cells in the Brain
Several subtypes, form a functional network
Functions of Astrocytes
The up and release chemicals at synapses
Provide neurons with substrates for ATP production
help maintain homeostasis in the ECF( take up K+ and H20)
Surround vessels
part of the blood brain barrier
influence vascular dynamics
Microglia
Specilaized immune cells that reside in the CNS
Serve to protect and preserve neuron cells from pathogens and facilitate recovery from metabolic insults
Ependymal Cells
Line fluid filled cavities in the brain and spinal cord
Protection
Chemical Stability
Clearing wastes
Peripheral Neuron Injury
CNS repair less likely to occur naturally, glia tend to seal off and form scar tissue. Lack Organelles. Reforms Synapse
Electrical Signals in Neurons
Neurons and muscle cells are “excitable” due to their ability to propagate electrical signals over long distances in response to a stimulus
Two factors influence the membrane potential
The uneven distribution of ions across the cell membrane (concentrations gradients)
Membrane permeability to those ions
What does the Nernest Equation describe
Nernest equation described the membrane potential that would result if the membrane were completely permeable to only one ion (the equilibrium potential for that ion)
Electrical Signals: GHK Equation
Predicts membrane potential that results from the contribution of all ions that can cross the membrane
Determined as the combined contribution of each ion (concentration x permeability) to the membrane potential
Different from Nernest Equation., which calculates the equilibrium potential for a single ions
Electrical signals in neurons
Resting membrane potential in most neurons is -70mV
Mainly due to K+
Na+ contributes slightly (very few Na+ leak channels)
Cl- minimally, equilibrium potential close to resting membrane potential
Ion movements create electrical signals
A change in the K+ concentration gradient or change in permeability to ions (Na+, K+, Ca2+ or Cl-) alters the membrane potential
- A significant change in membrane potential (-70mV to +30mV) does not indicate a change in concentration gradients for a given ion.
- very few ions need to move to alter the membrane potential (to alter the membrane potential by 100mV, 1 out of every 100,000 K+ ions must enter or leave the cell), which is a tiny fraction of total K+ in cell
- the concentration gradients for ions remain relatively constant during most alterations in membrane potential
5 major types of ion channels
Na+ channels
K+ Channels
Ca2+ channels
Cl- channel
Non covalent cation channels (allow Na+ and K+ to pass)
Conductance
Varies with the gating state of the channel
Channel protein isoform
Conductance
The ease with with which ions flow through a channel is known as the channels conductance
Types of Gated Channels
Mechanically Gated Channels
Chemically gated ion channels
Voltage gated channels
Mechanically gated channels
Open in response to physical forces (pressure or stretch), found in sensory neurons
Chemically gates ion channels
In neurons respond to ligands including extracellular neurotransmitters an neuromodulatorsor intracellular signalling modules
Voltage gated channels
Respond to changes in the cells membrane potential
Variation in gated channels
- Voltage for channel opening can vary from channel to channel
- the speed at which channels open or close varies
-many channels that open to depolarization will close during repolarization - Some channels spontaneously inactivate
Channel’s Subtypes
- Varying properties between subtypes
- Multiple isoforms that express different gating kinetics
- modifies by different proteins and pathways
Current flow and Ohm’s Law
- Current flow (I) is directly proportional to the electrical potential difference (in volts, V) between two points and inversely proportional to the resistance (R). I = V/R
Two sources of resistance in a cell:
Membrane resistance (Rm)
Internal resistance of the cytoplasm (Ri)
Membrane Resistance
Resistance of the phospholipid bilayer
Internal resistance of cytoplasm
Cytoplasmic composition and size of the cell
Electrical signals in neurons
Voltage changes across the membrane can be classifies in to 2 types of electrical signals:
Two types of electrical signals
Graded proteins
Actions potentials
Graded potentials
Variable strength signals that travel over short distances and lose strength as they travel. Can be depolarizing or hyper polarizing. If graded potentials create a large enough depolarization it can induce an Action Potential
Action Potential
Very brief, large depolarizations that travel for long distanced through a neutron without losing strength. Rapid signals over ling distances
Chanellopathies
Can disrupt how ions normally flow through the iron channel
Can alter channel activation
Can alter channel inactivation
Cystic fibrosis, congenital insensitivity to pain, muscle disorders
Graded Potentials
Graded because amplitude (size) is directly proportional to the strength of the stimulus and can vary
Decrease in strength as they spread out from the point of origin
Generated by chemically gated (Ligand gated) ion channels (CNS and efferent neurons)
Chemical, mechanical, thermal gated in sentry neurons
How do graded potentials lose strength
Current leak
Cytoplasmic resistance
Current leak
open channels allow ions to leak out
Depolarization
Excitatory Poatsynaptic Potential (EPSP)
Hyperpolarization
Inhibitory Postsynaptic Potential (IPSP)
Trigger Zone (Axon Hillock)
High concentration of voltage gated Na+ channels
If membrane potentials is 55mv an AP will be generated
Action Potential (AP)
Electrical signals of uniform strength (Aloo or none) that travel from the trigger zone to the axon terminals
Steps of Action Potential
Rising Phase
Falling phase
After Hyperpolarization phase
Rising Phase (Depolarization)
Depolarizing stimuli open voltage gated Na+ Channels (-55mV), allow Na+ to travel down electrochemical gradient
At +30mV Na+ channels inactivate
Falling phase (repolarization)
Voltage gated K+ also open in response to depolarization, but do so more slowly than Na+ change;s causing delayed efflux
After Hyperpolarization phase (Undershoot)
Voltage gated K+ do not immediately close when reaching -70mV causing membrane potential to dip below the resting membrane potential
Leak channels bring membrane potential back to -70mV
Na-KATPase returns ions to original compartments (this does not need to happen before another AP can be triggered)
Voltage Gated channels
The activation gate closes the channel at resting potential
Depolarizing stimulus arrives at the channel: Activation gate opens
With activation gate open, Na+ enters the cell
Inactivation gate closes and Na+ entry stops
During depolarization caused by K+ leaving the cell, the two gates reset to their original positions
Absolute Refractory Period
A second AP cannot be initiated 1-2 sec
Relative Refractory Period
A second AP can be initiated but requires a larger than normal depolarizing stimulus (Graded potential)
2-5msec
What is purpose of Refractory Period
Ensures an AP travels in one direction
Limits the rate at which signals can be transmitted down a neutron
- Information is often encoded in the frequency of AP’S
- Prevent excitotoxicity
Action potentials are conducted
AP’s travel over long distances without losing energy, a process referred to as conduction, size is identical at trigger zone and axon terminal
Two parameters determine the velocity of action potentials in mammalian neurons
The diameter of the axon
The resistance of the axon membrane to ion leakage
The diameter of Axon
A larger diameter axon will offer less internal resistance to current flow
- more ions will flow in a given time, bringing adjacent regions of the membrane to threshold faster
The resistance of the axon membrane to ion leakage
Current will spread to adjacent sections more rapidly if it is not lost via leak channels (myelin)
Conduction velocity is more rapidly in myelinated axon
AP conduction is more rapid in axons with high resistance membranes (decreased current leak)
Myelinated axons
have larger diameter axons
Unmyelinated axons
Have small diameter axons
Demyelination
- Only nodes contain Na+ channels, the AP cannot be maintained in the unmyelinated region due to a lack of Na+ channels
- Current leaks out of the unmyelinated region, increasing the likelihood that the wave of depolarization is subthreshlod when it reaches the next node containing Na+ channels
Normokalemia
When blood K+ is in the normal range
In normokalemia a suprathreshold (above threshold) stimulus will fire an action potential
Hyperkalemia
increased blood K+ concentration, brings the membrane closer to a threshold. Now a stimulus that would normally be subthreshlod can trigger an action potential
Hypokalemia
Decreased blood K+ concentration, hyper polarizes the membrane and. makes the neuron less likely to fire an action potential; in response to a stimulus that would normally be above the threshold
How do neurons communicate
Presynaptic cell (Neuron) to postsynaptic cell (Neuron, muscle, target cell)
Electrical synapses
Some CNS neurons, cardiac muscle, smooth muscle
Chemical Synapses
The majority of neurons in the nervous system use chemical signals to communicate from one cell to the next
- Electrical signals from the presynaptic cell is converted to a neurocrine signal that crosses the synaptic cleft and binds to a receptor on the post synaptic cell
Neurocrine
A chemical substance released from neurons used for cell to cell communication
Types of Neurocrines
Neurotransmitters
Neuromodulators
Neuroharmones
Neurotransmitters
A chemical substance released, acts on a postsynaptic cell in close vicinity and causes a rapid response in the postsynaptic cell
Neuromodulators
A chemical that is released, acts on a postsynaptic cell in close victim and causes a slow response in the postsynaptic cell
The same neurocrine can act as a neurotransmitter at one synapse and neuromodulator at another depending on the receptors present
Neuroharmones
Are secreted into the blood stream and act on targets throughout the body
Two categories of Neurocrine Receptors
Ionotropic receptors (ligand gated ion channels)
Metabotropic receptors (G- protein couples receptors)
Ionotropic Receptors
Ligand gated ion channels
Ligand binding to inotropic receptors causes a conformational change leading to the opening of channel
Can be specific for one ion (Na+, Ca2+, K+,Cl- ) or a non selective cation Channel
Mediate fast postsyanptic responses (neurotransmitter)
Metabotropic Receptors
G protein couples receptors
Slower responses (Neuromodulators)
Cytoplasmic tail of receptor is linked to three part membrane transducer protein (g-protein)
Ligand binding to metabotropic receptor leads to a G protein mediated cellular response
Two types of Metabotropic Receptors
I. Interact directly with ion channels
ii. interaction with a membrane bound enzyme
Interact directly with ion channels
Can lead to opening or closing of a channnel depending on G protein
Interaction with a membrane bound enzyme. Two main types:
A. Phospholipase C Signal Transduction Pathway
B. Adenyl cyclase signal transduction pathway
A. Phospholipase C Signal Transduction Pathway
Increase in intracellular Ca2+ mediates a cellular response
PKC can also mediate a cellular response
B. Adenyl Cyclase signal transduction pathway
PKA phosphorylates proteins to cause a cellular response
Fast responses are mediated by
Ion channels
Slow responses are mediated by
G protein coupled receptors
How does Neurotransmitter release occur
Occurs via Ca2+ mediated exocytosis
The pre synaptic terminal contains a high concentration of voltage gated Ca2+ channels
Steps of Neurotransmitter release
- An action potential depolarizes the axon terminal
- The depolarization opens voltage gated Ca2+ channels, and Ca2+ enters the cell
- Calcium entry triggers exocytosis of synaptic synaptic vesicle contents
- Neurotransmitter diffuses across the synaptic cleft and binds with receptors on the postsynaptic cell
- Neurotransmitter binding initiates a response in the postsynaptic cell
Termination of Neurotransmitter activity
- Neurotransmitters can be returned to axon terminals for reuse or transported into glial cells
- Enzymes inactivate neurotransmitters
- Neurotransmitters can diffuse out of the synaptic cleft
What happens if there is a increased AP firing
Leads to the greater influx of Ca2+ and increased neurotransmitter release
Convergence
Many presynaptic neurons may converge on one or a small number of postsynaptic neurons
Divergence
Neurons can have branching axons that contact many different postsynaptic neurons
