Neurophysiology Overview
Consistent with other systems of the human body, the nervous system structure (anatomy) and function (physiology) are intricately linked. Thus, a thorough knowledge of nervous system anatomy and histology is essential for understanding neurophysiology.
Cell Membrane
Neuron membranes are complex molecular structures mostly made up of lipids and proteins. They exhibit unique adaptations for cellular information-processing functions.
The membrane maintains the intracellular environment and separates the neuron from surrounding cells and the aqueous extracellular environment. Signaling must pass through the membrane.
Two opposing rows of phospholipid molecules comprise the neuron membrane:
The “head” end of each molecule is a polar (charged) phosphate group that is hydrophilic (attracted to aqueous environment).
The “tail” end of each molecule consists of two nonpolar (neutral) lipid extensions from the “head” that are hydrophobic (repelled by fluids) ().
Cholesterol molecules insert between the tails, preventing permeability of small water molecules and enhancing membrane flexibility.
Large proteins are interspersed between the phospholipid molecules of the neuron membrane (the number of different types of proteins in a cell membrane vary from approximately 100 to only a few). There are two primary classifications (see ):
Integral (transmembrane) proteins span the entire thickness of the cell membrane, enabling transport between extra- and intracellular environments. They are tightly embedded within and bound to the surrounding phospholipid molecules of the membrane.
Channel proteins allow small ions to passively move through the cell membrane (i. e., potassium [K+] leak channels) ().
Carrier proteins have ion-specific bonding sites which may transport ions passively (with gradient) or actively (against a gradient) across the membrane, depending on whether an energy source is available (i. e., sodium/potassium pump—ATP needed).
Peripheral proteins are loosely adherent to other membrane proteins or to the inner or outer membrane surface through hydrogen bonds.
This enables disconnection without affecting the structure of the membrane.
Action Potentials
When a neuron is resting (not firing), its axon membrane is polarized at -70 mV. This polarization results from intracellular fluid being relatively negative in comparison to the extracellular fluid. The polarized state is achieved by integral channel and carrier proteins in the cell membrane distributing ions across the membrane (e. g., sodium [Na+] potassium [K+] pump carrier proteins and K+ channel proteins). Ion movement creates electrical signals.
Resting potential is the difference in electrical charge between the extra- and intracellular sides of the neuron cell membrane (-70 mV).
Resting potential is created by:
Extra-/intracellular K+ concentration gradient.
Cell membrane permeability to K+, Na+, and chloride ions (Cl–).
Osmotic pressure (selective membrane permeability to water but not all solute particles).
Example: Na+–K+ pump carrier “transport” proteins move large numbers of Na+ out of the cell, creating a positive extracellular charge. Simultaneously, these proteins move some K+ into the cell’s cytoplasm. The cell becomes positive on the outside and negative on the inside because more Na+ ions are moved outside the cell than K+ ions are moved inside.
If a resting neuron is adequately stimulated, the neuron will transmit an impulse or signal known as an action potential.
An action potential is the movement of ions across the neuron’s membrane resulting in (1) rapid depolarization (charge moves toward 0 mV; i. e., no difference in charge) followed by (2) repolarization, (3) brief hyperpolarization (overshoot, meaning greater than -70 mV), and return to (4) normal resting potential of -70 mV. Nerve impulses are transmitted via action potentials.
Steps of an action potential (, also see example below):
Step #1: Depolarization—resultant from a “sufficient” stimulus
If the signal is strong enough for the membrane to reach the threshold level of -55 mV (threshold potential), an action potential will be triggered.
Depolarization is opening of neuron membrane Na+ channels, allowing extracellular Na+ to rush into the cell.
These Na+ channels are called voltage-gated ion channels because they can open and close in response to an electrical signal.
Threshold level stimulation activates opening of numerous voltage-gated ion channels. The amount of Na+ inside the cell increases and the cell membrane charge reverses (i. e., the inside of the cell becomes positively charged and the outside becomes negatively charged).
Step #2: Repolarization—when the intracellular membrane potential reaches approximately + 30 mV (“peak action potential”), the voltage-gated Na+ channels close and voltage-gated K+ channels open.
Potassium ions move outside the cell membrane and Na+ stays inside. This rapidly repolarizes the cell. However, the resulting polarization is now due to a greater amount of intracellular Na+ versus K+ (the Na+–K+ ion ratio is different compared to the initial “resting potential” polarization).
The cell membranes are unable to depolarize while the membrane potential is above -55 mV (occurs during depolarization and the initial part of repolarization).
Step #3: Hyperpolarization (i. e., the membrane potential moves lower than normal resting potential of > -70 mV; i. e., it “overshoots”). This is due to a brief increase in intracellular Na+ ions relative to the normal resting potential ratio of Na+–K+ ions.
The Na+–K+ pump moves intracellular Na+ ions out to the extracellular environment in exchange for K+ ions. This returns the neuron membrane to its normal intracellular Na+–K+ ion ratio and polarized resting state.
The Na+–K+ ion exchange helps to re-establish diffusion gradients and resting potential.
Step #4: Resting potential—the membrane potential returns to -70 mV. Resting potential is restored and the relative refractory period ends.
Important concepts of neuron signaling:
The refractory period ensures that an action potential will only travel forward. As an action potential moves forward along an axon, a new action potential is incapable of occurring until the membrane resting potential is re-established behind it. This limits the number of signals/impulses a neuron can generate over a period of time.
During the absolute refractory period, an action potential cannot be produced regardless of the stimulus strength. Voltage-gated Na+ channels are either already open or inactivated, thus making them incapable of producing an action potential.
During the relative refractory period, voltage-gated Na + channels are recovering from inactivation. If the neuron receives a sufficiently strong stimulus (greater than normal), it may generate another action potential.
Saltatory conduction (from Latin saltare, meaning “to leap”): Myelinated axons conduct signals faster than unmyelinated due to a phenomenon known as saltatory conduction.
In unmyelinated axons, Na+ channels must open sequentially along the axon for the signal to propagate.
Myelinated axons enable the signal to continue along the axon through myelin insulated segments without the need for channel opening. Sodium channel opening only occurs periodically at uninsulated spots along the axon known as “nodes of Ranvier” ().
Oligodendrocytes are cells in the central nervous system that myelinate multiple neurons.
Schwan cells are in peripheral nervous system; they myelinate individual neurons.
