Clinical meaning
Neuronal signaling is the fundamental electrochemical communication process of the nervous system, involving generation, propagation, and synaptic transmission of electrical impulses. At rest, neurons maintain a resting membrane potential of approximately -70 mV, established by the Na+/K+-ATPase pump (3 Na+ out, 2 K+ in per cycle) and the selective permeability of the membrane to K+ through leak channels (described by the Goldman equation). When a stimulus depolarizes the membrane to threshold (approximately -55 mV), voltage-gated sodium channels undergo rapid conformational change, opening and allowing Na+ influx that further depolarizes the membrane to approximately +30 mV (the rising phase of the action potential). Sodium channels then inactivate (ball-and-chain mechanism), and voltage-gated potassium channels open with a slight delay, allowing K+ efflux that repolarizes the membrane (falling phase). Brief hyperpolarization (undershoot to approximately -80 mV) occurs as K+ channels close slowly, creating the absolute and relative refractory periods that ensure unidirectional propagation. Action potential propagation along myelinated axons occurs via saltatory conduction: the myelin sheath (produced by Schwann cells in the PNS, oligodendrocytes in the CNS) insulates the axon between nodes of Ranvier, where voltage-gated sodium channels are concentrated. The action potential jumps from node to node, increasing conduction velocity from 0.5-2 m/s in unmyelinated C fibers to 80-120 m/s in large myelinated A-alpha fibers. Demyelination (as in multiple sclerosis or Guillain-Barré syndrome) disrupts saltatory conduction, causing slowed or blocked impulse transmission. At the synapse, depolarization of the presynaptic terminal opens voltage-gated calcium channels; Ca2+ influx triggers vesicle fusion with the presynaptic membrane via SNARE proteins (synaptobrevin, syntaxin, SNAP-25) and release of neurotransmitters (acetylcholine, glutamate, GABA, dopamine, serotonin, norepinephrine) into the synaptic cleft. Neurotransmitters bind postsynaptic receptors, producing either excitatory postsynaptic potentials (EPSPs, via glutamate AMPA/NMDA receptors allowing Na+/Ca2+ influx) or inhibitory postsynaptic potentials (IPSPs, via GABA-A receptors allowing Cl- influx). Temporal and spatial summation of EPSPs and IPSPs at the axon hillock determines whether the postsynaptic neuron reaches threshold and fires.