Action Potential Propagation: How Signals Travel Along Neurons

Synaptic transmission converts electrical signals (action potentials) into chemical signals that cross the synaptic cleft. When an action potential reaches the axon terminal, voltage-gated calcium channels open, allowing calcium influx. Calcium binds to synaptic vesicles, triggering exocytosis of neurotransmitters. The neurotransmitter diffuses across the synaptic cleft and binds to postsynaptic receptors. For cholinergic synapses, acetylcholine binds ligand-gated sodium channels, causing sodium influx and depolarization. This can trigger potassium channels to open, changing membrane voltage and potentially initiating a new action potential in the postsynaptic cell.

Synaptic transmission converts electrical signals to chemical signals at the synapse. When action potentials reach the presynaptic terminal, synaptic vesicles containing neurotransmitters (like acetylcholine) migrate toward the membrane, fuse, and release contents into the synaptic cleft. The electrical signal (action potential frequency) is converted to chemical signal (neurotransmitter concentration), then back to electrical signal in the postsynaptic cell. Acetylcholinesterase breaks down acetylcholine after signaling, allowing vesicle recycling. This process enables precise, rapid communication between neurons and between neurons and muscles.

At the synaptic terminal, the electrical signal of an action potential is converted to a chemical signal. Neurotransmitter-filled vesicles fuse with the presynaptic membrane and release their contents into the synaptic cleft. These neurotransmitters then diffuse across the gap and bind to receptors on the postsynaptic neuron's dendrites, passing the message chemically.

Synaptic transmission converts electrical signals to chemical signals and back: An action potential arrives at the axon terminal, causing calcium channels to open and calcium to enter. This triggers vesicles containing neurotransmitters (e.g., acetylcholine) to fuse with the presynaptic membrane and release neurotransmitters into the synaptic cleft. Neurotransmitters bind to receptors on the postsynaptic membrane, causing ion channels to open and generating a postsynaptic potential.

Synaptic transmission converts electrical signals to chemical signals. When an action potential arrives at the axon terminal, it opens calcium channels. Calcium enters the terminal (since it's more concentrated outside), triggering exocytosis of synaptic vesicles containing neurotransmitters. Neurotransmitters diffuse across the synaptic cleft and bind to receptors on the postsynaptic membrane, opening ion channels and continuing the signal transmission.

EPSP (Excitatory Postsynaptic Potential) occurs when sodium ions flow into the postsynaptic membrane, depolarizing it and bringing it closer to the threshold for action potential generation, while IPSP (Inhibitory Postsynaptic Potential) occurs when chloride ions flow in, hyperpolarizing the membrane and moving it further from threshold; neurons integrate multiple EPSPs and IPSPs through spatial and temporal summation at the axon hillock, where the net effect determines whether an action potential will be generated, with EPSPs promoting firing and IPSPs reducing it.

Excitatory postsynaptic potentials (EPSP) and inhibitory postsynaptic potentials (IPSP) are graded potentials that develop on the postsynaptic membrane during synaptic transmission; EPSP causes depolarization (moving potential toward less negative values, e.g., from -70mV to -60mV) through mechanisms like sodium channel opening or potassium channel closure, while IPSP causes hyperpolarization (moving potential toward more negative values, e.g., from -70mV to -80mV) through chloride channel opening or potassium channel opening; these graded potentials travel with decrement, can be summed spatially (multiple synapses activating simultaneously) or temporally (repeated activation of the same synapse), and their net summation determines whether an action potential is generated at the axon hillock.

Neurons integrate incoming signals through algebraic summation at the axon hillock, where excitatory postsynaptic potentials (EPSPs) and inhibitory postsynaptic potentials (IPSPs) combine; if the total EPSP reaches or exceeds the threshold, an action potential is generated, otherwise no signal passes. This integration process is demonstrated through experiments showing that inhibitory neurotransmitters like GABA cause hyperpolarization (IPSP), while excitatory neurotransmitters like acetylcholine cause depolarization (EPSP), and that drugs like benzodiazepines enhance GABA's binding to post-synaptic receptors, increasing inhibitory effects.

Neurons integrate thousands of inputs through summation at the axon hillock. Excitatory post-synaptic potentials (EPSPs) increase membrane potential toward threshold, while inhibitory post-synaptic potentials (IPSPs) decrease it. If combined inputs reach threshold (-60 mV), an action potential is generated; otherwise, none occurs. This integration represents the fundamental decision-making process of the nervous system. Inputs arrive from diverse sources, some excitatory and some inhibitory, and their net effect determines whether the neuron fires.

Synaptic integration is the process by which neurons combine multiple inputs. The postsynaptic cell sums excitatory and inhibitory postsynaptic potentials. Excitatory postsynaptic potentials (EPSPs) depolarize the postsynaptic membrane, bringing it closer to threshold. Inhibitory postsynaptic potentials (IPSPs) hyperpolarize the membrane, moving it away from threshold. If the total depolarization reaches threshold (-55 mV), an action potential is generated. Acetylcholine effects are transient because acetylcholinesterase enzyme breaks down acetylcholine in the synaptic cleft, closing receptor channels and returning the membrane to resting state.

The myelin sheath is a fatty insulating layer around axons that enables saltatory conduction, where impulses jump between nodes of Ranvier. Thicker myelin means faster conduction. Diseases damaging myelin impair neural function: multiple sclerosis (central nervous system inflammation), Guillain-Barré syndrome (peripheral nervous system attack), and leukodystrophies. In the CNS, oligodendrocytes provide myelin; in the PNS, Schwann cells do. Local anesthesia works by blocking sodium channels, preventing impulse propagation.

In multiple sclerosis, demyelination of myelinated axons causes conduction block because the loss of myelin sheath eliminates the insulating properties that normally increase membrane resistance and decrease capacitance, preventing adequate current flow between nodes of Ranvier; this is why symptoms worsen with heat (Uhthoff's phenomenon) and why potassium channel blockers like aminopyridines can help by blocking the exposed potassium channels and broadening the action potential to facilitate conduction through demyelinated segments.

Myelination creates insulating layers around axons, enabling saltatory conduction where signals jump between nodes of Ranvier. This increases conduction speed from 0.25 m/s in unmyelinated to 100 m/s in myelinated neurons while reducing energy expenditure. Local anesthetics like lidocaine block voltage-gated sodium channels, preventing pain signal transmission. Potassium channel blockers increase cellular excitability by preventing potassium efflux. Electrolyte imbalances significantly affect excitability: hypocalcemia (low calcium) increases excitability causing tetany, while hyperkalemia (high potassium) decreases excitability potentially causing cardiac arrest. Multiple sclerosis is an autoimmune demyelinating disease where the immune system attacks myelin sheaths, disrupting saltatory conduction. Optic neuritis is often an early symptom due to the optic nerve's heavy myelination for rapid visual signal transmission.

Local anesthetics inhibit voltage-gated sodium channels to prevent action potential conduction. They cross cell membranes as lipid-soluble (non-ionized) forms, binding to sodium channels and stabilizing them in the inactivated state. Classified as esters (metabolized by plasma esterases, e.g., procaine, lidocaine) or amides (metabolized by liver P450 enzymes, e.g., bupivacaine). Cocaine, an ester, causes severe vasoconstriction and nasal septal perforation. Bicarbonate addition increases pH, decreases pKa, and increases the unionized fraction for faster onset. Potency correlates with lipid solubility and protein binding.

Demyelinating diseases impair signal transmission by destroying myelin sheaths while preserving axons. Unlike axonal neuropathies, these conditions primarily affect conduction velocity rather than amplitude. Normal conduction velocity is approximately 50 m/s in upper extremity nerves; demyelinating diseases cause significant slowing (e.g., 30 m/s or lower). Conduction block represents focal myelin loss creating a segment of impaired signal transmission. In Guillain-Barré syndrome, conduction block produces characteristic 50% response reduction when stimulating proximal to the block while maintaining normal responses distal to it. Since axons remain intact, remyelination allows functional recovery.