1. Nervous System and Muscle Physiology Flashcards
Neuron: Regions
Cell body (soma)
Dendrites (impulses to cell body)
Axon hillock (initiation of AP)
Axon (impulses away from body)
60-40-20 Rule
60% of body weight is water
40% of body weight is ECF
20% of body weigh is ICF
ECF
75% interstitial fluid
25% plasma
Separated by capillary wall
Potassium (K)
Higher inside cell (ICF)
Circle K
Moves out of cell
Greatest influence on resting membrane potential
Sodium (Na)
Higher outside cell (ECF)
Moves into cell
Chloride (Cl)
Higher outside cell (ECF)
Moves into cell
The membrane must be more permeable to some ions and less permeable to others
Number and opening probabilities of ion channels are key
Primary Active Transport
Directly requires ATP
Ex: Na K ATPase
Secondary Active Transport
Utilizes ATP indirectly
Ex: Na and glucose movement into cell - relies on gradient created by Na K ATPase
Facilitated Diffusion
Passive movement of molecules across membrane with the help of a membrane protein
Ex: glucose
Cell Membrane Transport: Across Membrane
Endocytosis (pinocytosis, phagocytosis)
Exocytosis
Cell Membrane Transport: Through Membrane
Diffusion
Osmosis
Protein mediated transport (primary active, secondary active, facilitated diffusion)
Simple Diffusion
Linear
Protein Mediated Transport
Curve with a plateau - exhibits saturation
Membrane Ion Channels
Selective
Sometimes open, sometimes closed
- Voltage operated
- Receptor (ligand) operated
- Stretch activated
- Ungated (open all the time)
Conductance
The number of channels that are open in a membrane
Resting Membrane Potential
Potential difference that exists across the membrane of excitable cells
Established by diffusion potentials (K concentration gradient)
Diffusion Potentials
Depends on:
- ions present
- permeability (conductance) of each ion
- electrochemical gradients of each ion
NaKATPase
Electrogenic (transfers positive charge out cell, unequal)
3 Na out, 2 K in
Necessary to create and maintain K concentration gradient - establishes resting membrane potential
Resting Membrane Potential: K
K leaves the cell (leaving being negative charge)
Negative charges build up inside membrane - establishing RMP
Inside: -70
Outside: 0
Ion Equilibrium Potentials
Na = +65 K = -85 Cl = -90
Action Potential
Involves voltage gated channels (Na)
All or none phenomenon (has a threshold (-50))
Non decremental propagation
- occurs along axon without decay
- same strength at beginning and end
Action Potential: Phases
- upstroke: gNa»_space; K
- repolarization: gK>gNa
- after hyperpolarization: gK»gNa
During which interval of the action potential would the O2 consumption in milliliters of O2 most exceed the resting level?
When the NaK pump reestablishes gradients across the membrane (return to rest) - ATP usage
Myelinated Fibers
Saltatory conduction (node to node)
Nodes contain high concentration of voltage gated Na channels
Insulation: good for conduction
Skipping
Unmyelinated Fibers
Electrotonic conduction
Low density of voltage gated Na channels spread throughout axon
Less efficient/fast
Large diameter = faster conduction
Walking one foot in front of other
Multiple Sclerosis
MRI: gadolinium enhancing brain lesions
CSF: oligoclonal IgG bands (Dawson’s fingers around periventricular veins - inflammation)
Autoimmune disease
Loss of myelin from CNS axons - replaced by scar tissue (sclerosis)
- Difficulty walking due to demyelinated axons (Loss of current at demyelinated segment - falls below threshold - no AP - weakness)
- Deep tendon reflexes working early in disease
- Eventual degeneration of nerves will lead to muscle atrophy and weakness
Pre-synaptic Neuron
Contains NT
Post-synaptic Neuron
Contains R
Synaptic Delay
1-5 msec for chemical transmission to occur
No physical continuity bt pre and post synaptic neurons
Synapse: excitatory c. inhibitory
Depends on type of receptor present - not the NT
Amplification
Release of more neurochemical transmitter
More NT = more R bound = bigger response
Characteristics of Neurotransmitters
Must meet all 4:
1. synthesized in presynaptic cell, enzymes for synthesis must be present in neuron
- must be released by presynaptic cell with stimulation in sufficient quantity to elicit postsynaptic response
- Mechanisms for removal or inactivation must exist
- when applied exogenously, must mimic in vivo response
Synaptic Transmission
- AP at axon terminal
- voltage gated Ca channels open
- Ca enters cell
- Ca signals to vesicles
- Vesicles move to membrane
- Docked vesicles release NT - exocytosis
- NT diffuses across synaptic cleft - binds to receptors
Postsynpatic Potentials
EPSP (depolarization)
-helps Na and K move
IPSP (hyperpolarization)
-helps Cl or K move
Graded Potentials
Electrotonic conduction
Chemical gated channels
No refractory period
No threshold
Amplitude dependent on magnitude of stimulus
Exhibits decremental conduction
Choline Esters
Small molecule, rapidly acting
Acetylcholine
Receptors:
- nicotinic (excitatory)
- muscarininc (inhibitory)
Biogenic Amines
Small molecule, rapidly acting
Dopamine Epinephrine Histamine Norepinephrine Serotonin
Receptors (for epi,norepi)
- alpha R
- beta R
Amino Acids
Small molecule, rapidly acting
y aminobutyric acid (GABA)
glutamate
glycine
Neuropeptides
Larger, longer acting
Some: ACTH Endorphins Oxytocin Secreting Vasopressin
Synaptic Transmission at Neuromuscular Junction
- AP travels down motoneuron to presynaptic terminal
- Depolarization opens Ca2+ channels
- ACh released into synaptic cleft (exocytosis, ATP and Ca2+ requiring)
- ACh R binding at motor end plate
- Na entry, K efflux via open channel
- Motor end plate depolarization (EPP)
- ACh degradation via acetylcholineesterase, choline reuptake via Na/choline symport
Myasthenia Gravis
Muscle weakness
Endrophonium (tensilon) test: positive
Plasma testing: antibodies against ACh R
Autoimmune disease
Destruction of Ach receptors on motor end plates
Normal Ach release
Failure does not occur until 70% of Ach R damaged (safety factor)
Safety Factor
Measures how much larger EPP is compared to threshold
Normally, magnitude of EPP is large - guarantees depolarization to threshold
Agents Affecting Neuromuscular Transmission
Botulinum toxin (prevents Ach release)
Hemicholinium (blocks Na/choline transporter)
Curare (competition for binding on motor end plate)
AChE inhibitors (prevents AChE from breaking down ACh)
Flaccid Paralysis
Muscles cannot contract
Limp, flappy
Botulinum toxin
Spastic Paralysis
Continuous muscle contraction
Rigid
AP and the Sarcomere
AP travels inward through sarcomere through T tubules and along surface of muscle fiber
Contraction of Skeletal Muscle
A band: no change
I band: shortens
H zone: shortens
Z lines: closer together
Excitation Contraction Coupling in Skeletal Muscle
- AP in muscle membrane
- Depolarization of T tubules
- Opens SR Ca2+ release channels
- Increase intracellular Ca2+
- Ca2+ binds troponin C
- Tropomyosin moves - actin myosin interaction
- Cross bridge cycling and force generation
- Ca2+ reaccumulated by SR –> relaxation
Continues as long as intracellular Ca is high
Muscle Cell At Rest
Cytosolic Ca2+ low
Myosin and actin dissociated
Myosin head holds ADP, Pi
Binding site on actin covered
Muscle Cell After Increased Intracellular Ca
Ca2+ binds to troponin C
Myosin binding sites uncovered
Myosin heads bind to actin
Cross bridges formed
Cross Bridging Cycle: Power Stroke
Force produced by myosin head pivots
ADP and Pi released
Bond bt actin and myosin stronger
Cross bridges pivot (~45 degrees)
Tension produced - “twitch”
Contractile force is proportional to number of cross bridges formed
Cross Bridging Cycle: Myosin Release
ATP binds to myosin
Cross bridges break
If ATP supply fails…
cross bridges are maintained – rigor mortis
Cross Bridge Cycle: Regeneration of Activated Myosin
ATP hydrolyzed to ADP and Pi - stay bound
Myosin re-energized
Myosin displaced toward + end of actin
Next cross bridge cycle can occur
Cycle repeats as long as Ca is bound to troponin
Relaxation
Depends on prompt Ca removal
Drop in Cytosolic Ca Levels
Ca dissociates from troponin C
Tropomyosin/troponin complex to original conformation
Binding site on actin sterically blocked by tropomyosin
Sarcomere
Basic contractile unit
Delineated by Z disks
Thick filaments Thin filaments M line H zone A band I band
Temporal Sequence of Events in Skeletal Muscle Contraction
- AP
- Rise in intracellular Ca
- Tension
Duchenne’s Muscular Dystrophy
Poor muscle coordination
Weak muscles/grip strength
Hypertrophied muscles
Plasma analysis: elevated creatine kinase
Muscle biopsy
Loss of dystrophin
Creatine Kinase
Elevated when muscles are damaged
Duchenne’s Muscular Dystrophy: Dystrophin
Structural link bt cytoskeleton and muscle cell
Without: alters transmission of tension
- damage to cell membrane (sarcolemma wilts/becomes unstable)
- creatine kinase leaks out of cell
- muscle weakness
Pseudohypertrophy of calf muscles due to inflammatory response
Replacement of damaged muscle cells with scar tissue
Calves look okay but really its scar tissue
