7.1 Nerve Physiology, Conduction & Transmission

Resting Membrane Potential & the Action Potential

The resting membrane potential (RMP) of a typical neuron is approximately -70 mV, with the inside negative relative to the outside. This potential is generated by two features working together: (1) concentration gradients established by the Na+/K+-ATPase, which pumps 3 Na+ out and 2 K+ in per ATP, and (2) the membrane's much higher permeability to K+ at rest, owing to abundant K+ leak channels. Because K+ moves outward down its gradient, the interior loses positive charge until the K+ equilibrium potential (~-90 mV) is approached; the small residual Na+ leak pulls the actual RMP to ~-70 mV. The Nernst equation predicts the equilibrium potential for a single ion, and the Goldman-Hodgkin-Katz equation extends this to multiple ions weighted by permeability.

The action potential (AP) is an all-or-none regenerative depolarization that propagates along the axon. It proceeds in four phases:

1. Depolarization to threshold (~-55 mV): a small stimulus opens enough voltage-gated Na+ channels to trigger regenerative opening.
2. Rising phase: voltage-gated Na+ channels open rapidly; Na+ influx drives the membrane toward the Na+ equilibrium potential (~+60 mV). The peak reaches roughly +30 to +40 mV.
3. Repolarization: Na+ channels inactivate (a ball-and-chain plug blocks the pore), and delayed-rectifier voltage-gated K+ channels open, allowing K+ efflux.
4. Afterhyperpolarization: K+ channels close slowly, transiently driving the membrane below RMP toward the K+ equilibrium potential.

The absolute refractory period corresponds to Na+ channel inactivation (no stimulus, however strong, can fire a second AP). The relative refractory period follows, during which a larger-than-normal stimulus is required because some K+ channels remain open and the membrane is hyperpolarized.

Conduction Velocity: Diameter and Myelination

Conduction velocity depends on two axon properties. First, larger axon diameter reduces axial resistance to current flow, allowing local circuit currents to spread farther and depolarize the next stretch of membrane faster. Second, myelination wraps the axon in a multi-lamellar lipid sheath that increases membrane resistance and decreases capacitance, so that depolarizing current spreads rapidly along the internode with little leak.

Saltatory Conduction

In myelinated axons, voltage-gated Na+ channels cluster at the nodes of Ranvier (short unmyelinated gaps ~1 µm long) and are sparse under the myelin. An AP generated at one node produces local circuit current that depolarizes the next node to threshold, so the impulse appears to jump node-to-node. This is saltatory conduction, and it confers two advantages: faster conduction for a given axon caliber, and metabolic economy (the Na+/K+-ATPase works only at nodes rather than along the entire axon). Schwann cells myelinate one segment each in the peripheral nervous system (PNS), whereas oligodendrocytes wrap multiple CNS axons with a single cell. Demyelinating diseases—multiple sclerosis (CNS) and Guillain-Barré syndrome (PNS)—slow or block conduction by disrupting the myelin sheath.

Synaptic Transmission

Most synapses in the mammalian nervous system are chemical synapses. The presynaptic terminal, or bouton, contains synaptic vesicles loaded with neurotransmitter. When an AP invades the terminal, it opens voltage-gated Ca2+ channels (primarily N- and P/Q-type); Ca2+ influx triggers vesicle fusion via the SNARE complex (synaptobrevin on the vesicle, syntaxin and SNAP-25 on the membrane). Neurotransmitter diffuses across the synaptic cleft (~20-40 nm) and binds ligand-gated ion channels (ionotropic receptors) or G-protein-coupled receptors (metabotropic receptors) on the postsynaptic membrane.

Neurotransmitters

Key small-molecule neurotransmitters include acetylcholine (ACh; neuromuscular junction, autonomic ganglia, parasympathetic effectors), glutamate (the dominant excitatory transmitter in the CNS), GABA (gamma-aminobutyric acid; the dominant inhibitory transmitter), glycine (inhibitory in the spinal cord), and the catecholamines dopamine, norepinephrine, and epinephrine. Serotonin (5-HT) is an indolamine modulating mood, sleep, and gastrointestinal function. Peptide transmitters such as substance P and endorphins often co-localize with small-molecule transmitters.

EPSPs and IPSPs

An excitatory postsynaptic potential (EPSP) is a small depolarization (~0.5-1 mV) produced by opening nonspecific cation channels (e.g., AMPA receptors passing Na+ and K+). An inhibitory postsynaptic potential (IPSP) is a hyperpolarization produced by opening Cl- channels (GABAA or glycine receptors) or K+ channels (GABAB receptors). A single EPSP is far below threshold, so the neuron must summate inputs:

• Spatial summation: simultaneous EPSPs from multiple presynaptic neurons add at the soma.
• Temporal summation: repeated EPSPs from one presynaptic neuron arrive before the prior one decays.

The axon hillock (initial segment) integrates EPSPs and IPSPs; when the membrane reaches threshold (~-55 mV), an AP is initiated and propagates down the axon. Inhibitory inputs are frequently targeted to the soma or proximal dendrites where they can most effectively shunt excitatory current—a phenomenon called shunting inhibition.

Clinical and Exam Relevance

PA-CAT Physiology questions commonly test the ionic basis of each AP phase, the role of the Na+/K+-ATPase in maintaining gradients (versus its indirect contribution to the AP itself), the effect of Ca2+ at the presynaptic terminal, and the consequences of demyelination. Remember that tetrodotoxin and local anesthetics block voltage-gated Na+ channels from the outside, while tetraethylammonium blocks voltage-gated K+ channels. Botulinum toxin cleaves SNARE proteins, preventing ACh release at the neuromuscular junction; alpha-latrotoxin (black widow spider) causes massive ACh release. Per the PA-CAT Bulletin of Information, rev. 20240815, Physiology comprises 16% of the exam (39 scored-equivalent items), and neural conduction and synaptic transmission are explicitly listed under the Nervous System group in Table 4.