Nerve Physiology and Synaptic Transmission
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Nerve Physiology and Synaptic Transmission — Key Facts for FMGE Core concept: Neurons generate action potentials via voltage-gated Na and K channels; synapses transmit signals via neurotransmitters High-yield point: Action potential propagation follows all-or-none law; refractory periods ensure unidirectional flow ⚡ Exam tip: The absolute refractory period corresponds to Na channel inactivation; relative refractory period corresponds to K channel activation
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Nerve Physiology and Synaptic Transmission — FMGE Study Guide
Resting Membrane Potential
Ionic Distribution
- Intracellular: High K (140 mM), low Na (10-15 mM), high protein anions
- Extracellular: High Na (145 mM), High Cl (110 mM), low K (3-5 mM)
- Cause: Na/K ATPase + K leak channels
Origin of Resting Potential
- K leak channels allow K to flow out down its concentration gradient
- Creates negative charge inside (cations lost = more negative)
- Equilibrium reached when electrical gradient balances chemical gradient
- Goldman equation: Takes permeability of all major ions into account
- At rest: K permeability >> Na permeability → resting potential close to K equilibrium potential (-90 mV)
- Actual resting potential (-70 mV) is less negative than Ek because some Na leaks in
Action Potential
Phases
Resting state: All voltage-gated channels closed; Na channels deactivated
Depolarization (Phase 0):
- Stimulus reaches threshold (-55 mV)
- Voltage-gated Na channels open rapidly (fast Na channels)
- Na influx → rapid depolarization toward +30 mV (Na equilibrium potential)
- All-or-none: Either reaches threshold or doesn’t fire
Repolarization (Phase 1):
- Na channels inactivate (fast inactivation)
- K channels open (delayed rectifier K channels)
- K efflux → rapid return toward resting potential
After-hyperpolarization (Phase 2/Hyperpolarization):
- K channels remain open slightly longer
- Membrane becomes slightly more negative than resting potential
- Overshoot: Brief hyperpolarization
Return to resting (Phase 3):
- All channels return to resting state
- Na/K ATPase restores ionic gradients (slowly - over minutes)
Properties
Threshold: -55 mV (must reach this to fire) Peak: +30 mV Duration: 1-2 ms in neurons Propagation: Spread to adjacent areas via local currents
Refractory Periods
Absolute refractory period:
- During depolarization and early repolarization
- Na channels are inactivated (cannot open again no matter how strong stimulus)
- No action potential can be initiated during this period
- Determines maximum firing frequency
Relative refractory period:
- During after-hyperpolarization
- Some Na channels have returned from inactivation but K channels still open
- Can initiate AP with stronger-than-normal stimulus
- Higher threshold during this period
Propagation
Unmyelinated fibers:
- Action potential regenerates at each point along the axon
- Slow conduction (1 m/s in small fibers)
Myelinated fibers (saltatory conduction):
- Myelin insulates axon (lipid - poor conductor)
- Currents “jump” between Nodes of Ranvier ( Nodes of Ranvier)
- Nodes have high density of voltage-gated Na channels
- Much faster conduction (50-150 m/s)
Factors affecting conduction velocity:
- Axon diameter (larger = faster)
- Myelination (myelinated = faster)
- Temperature (higher = faster within physiological range)
Classification of Nerve Fibers
| Type | Function | Diameter | Conduction |
|---|---|---|---|
| Aα | Muscle spindles, motor | 13-20 μm | 70-120 m/s |
| Aβ | Touch, pressure | 8-13 μm | 40-70 m/s |
| Aγ | Muscle spindle (intrafusal) | 4-8 μm | 15-40 m/s |
| Aδ | Pain, temperature (sharp) | 1-4 μm | 6-30 m/s |
| B | Preganglionic autonomic | 1-3 μm | 3-15 m/s |
| C | Pain, temperature (dull), postganglionic autonomic | 0.5-1.5 μm | 0.5-2 m/s |
Synaptic Transmission
Synapse Structure
- Presynaptic terminal: Contains synaptic vesicles with neurotransmitter
- Synaptic cleft: 20-40 nm gap
- Postsynaptic membrane: Contains receptors for neurotransmitter
Steps in Synaptic Transmission
- AP arrives at presynaptic terminal
- Voltage-gated Ca²⁺ channels open → Ca²⁺ influx
- Ca²⁺ triggers vesicle fusion with presynaptic membrane
- Neurotransmitter released into synaptic cleft
- Neurotransmitter binds to postsynaptic receptors
- Postsynaptic response: Excitatory (depolarization) or inhibitory (hyperpolarization)
- Neurotransmitter removed: Reuptake, degradation, diffusion
Types of Synapses
Electrical synapses:
- Gap junctions (connexons)
- Direct ionic communication
- Bidirectional, very fast
- Found in some CNS neurons, heart, smooth muscle
Chemical synapses:
- Neurotransmitter-mediated
- Unidirectional
- Slower but allows amplification and modulation
- Most synapses in CNS
Neurotransmitters
Excitatory neurotransmitters:
- Glutamate: Major excitatory in CNS; NMDA, AMPA, kainate receptors
- Acetylcholine: At NMJs, autonomic ganglia, CNS
Inhibitory neurotransmitters:
- GABA: Major inhibitory in CNS; GABA-A (Cl channel), GABA-B (K channel, Gi)
- Glycine: Major inhibitory in spinal cord; Cl channel
Others:
- Dopamine: D1 (excitatory), D2 (inhibitory) - reward, movement
- Norepinephrine: Locus coeruleus - arousal, attention
- Serotonin: Mood, sleep, appetite
- Substance P: Pain transmission
- Endorphins: Pain modulation, pleasure
Synaptic Integration
EPSP (Excitatory Postsynaptic Potential):
- Na or Ca influx → depolarization
- Graded (size proportional to stimulus)
- Additive (spatial summation)
- Rapidly decaying
IPSP (Inhibitory Postsynaptic Potential):
- Cl influx or K efflux → hyperpolarization
- Graded, additive
- Can also prevent EPSPs (shunting inhibition)
Summation:
- Spatial: Multiple synapses fire simultaneously
- Temporal: Same synapse fires rapidly in succession
- Integration: At axon hillock - determines if AP fires
Postsynaptic Receptors
Ionotropic receptors (ligand-gated ion channels):
- Fast response (milliseconds)
- Direct channel opening
- Examples: NMDA, AMPA (glutamate), GABA-A (Cl), nicotinic ACh (Na)
Metabotropic receptors (GPCR):
- Slower response (seconds to minutes)
- Second messenger systems
- Examples: Muscarinic ACh, GABA-B, dopamine receptors
Neuromuscular Junction
- Motor neuron axon terminal meets skeletal muscle fiber
- Motor end plate: Specialized region of muscle membrane
- ACh released → binds nAChR → Na influx → end plate potential (EPP)
- Miniature EPPs: Spontaneous vesicle release
- Safety factor: EPP always > threshold → always triggers AP
- Myasthenia gravis: Autoantibodies against AChR → fatigable weakness
- Lambert-Eaton: Antibodies against presynaptic Ca channel → weakness, improves with exercise
Nerve Conduction Studies
Latency: Time from stimulus to response Amplitude: Size of response Velocity: Calculated from distance and latency Demyelination: Slowed conduction, temporal dispersion, prolonged latencies
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