What is nerve cell physiology?

Nerve Cell Physiology

Nerve cells (neurons) communicate through a sophisticated combination of electrical and chemical signaling mechanisms, where electrical signals propagate within the neuron via charged particles, and chemical neurotransmitters facilitate communication between neurons at specialized junctions called synapses. 1

Fundamental Electrical Properties

Transmembrane Current Generation

• Transmembrane currents generate all electrical and magnetic signals recorded from the brain, passing through neuronal and glial cell membranes via both active and passive mechanisms, including capacitive coupling between conductive elements. 2
• The neuronal membrane functions as a capacitor, with ion channels acting as resistors that allow passive flow of charge (particularly Na+ and K+ ions) along electrochemical gradients. 3
• Cable theory dictates that the sum of transmembrane ionic and capacitive currents across the entire cellular surface must equal zero—currents entering the cell are balanced by currents leaving at other locations. 2

Action Potential Propagation

• Within the neuron, electrical signals driven by charged particles allow rapid conduction from one end of the cell to the other, with the action potential representing a non-linear, self-propagating, regenerative wave of electrical activity. 1, 3
• The signal propagates through both active and passive conduction mechanisms dependent on local current flow by diffusion of Na+ ions in the neuronal cytoplasm. 3
• Propagation occurs in both myelinated and unmyelinated membranes, with successive regeneration by means of action potentials necessary for long-distance signal transmission. 4

Nerve Fiber Classification and Characteristics

Myelinated Fibers (Type A and B)

• Type A myelinated fibers have large diameters and fast conduction velocities of 14-32 m/s, primarily affecting proprioception, vibratory sense, and light touch. 5
• Type B preganglionic autonomic fibers have intermediate conduction velocity with a threshold of activation approximately 10 times greater than type A fibers. 5
• Large fiber neuropathy (Type A) shows abnormalities in nerve conduction studies when damaged. 5

Unmyelinated Fibers (Type C)

• Type C unmyelinated fibers have small diameters (<2 μm) and slow conduction velocities of 0.8-1.5 m/s, constituting the majority of afferent fibers innervating the respiratory tract and lungs. 2, 5
• These fibers have a threshold of activation approximately 46 times greater than type A fibers and transmit chronic pain, temperature, and autonomic signals. 5
• C-fibers are distinguished by their relative insensitivity to mechanical stimulation but high sensitivity to chemical mediators including bradykinin, capsaicin, protons (via TRPV1 channels), and irritants like ozone and allyl isothiocyanate (via TRPA1 channels). 2
• Small fiber neuropathy (C and Aδ) affects temperature and pain perception, presenting with painful sensations such as burning in hands and feet. 5

Synaptic Communication Mechanisms

Chemical Neurotransmission

• Communication between neurons occurs at synapses—tiny gaps where presynaptic and postsynaptic neurons come within nanometers of one another to allow chemical transmission. 1
• The presynaptic neuron releases neurotransmitters that bind to specialized receptor proteins on the postsynaptic neuron, altering its function. 1
• Synaptic transmission is characterized by fast and localized transfer of signals from presynaptic neurons to postsynaptic cells, accounting for the brain's ability to rapidly process information. 6

Receptor Types

• Two types of neurotransmitter receptors exist: ligand-gated ion channels (permitting rapid ion flow directly across the cell membrane) and G-protein-coupled receptors (initiating chemical signaling cascades within the cell). 1
• Hundreds of molecules act as neurotransmitters in the brain, ranging from classical fast transmitters like glycine and glutamate to neuropeptides, lipophilic compounds, and gases such as endocannabinoids and nitric oxide. 6

Membrane Structure and Function

Lipid Bilayer Organization

• The neuronal plasma membrane consists of lipids forming a bilayer structure maintained by cohesive forces, providing the basic framework for membrane function. 7
• The membrane exhibits intrinsic biophysical properties as a biological bilayer, with the collective material and physico-chemical properties of the lipid bilayer determining various physical manifestations of neuronal activity. 3

Membrane Proteins

• Both peripheral and integral membrane proteins are responsible for the specificity and functional differentiation of neurons, with many nervous system disorders originating from defective synthesis or incorrect functioning of particular membrane proteins. 7
• The membrane skeleton consists of cytoskeletal protein polymers, particularly actin fibrils, which contribute to the multiphysics of nerve signal propagation. 3

Field Potential Generation and Spatial Organization

Extracellular Signal Characteristics

• Field potentials sum activity from all electrically active membranes and transmembrane current generators in space and time, from axon terminals to soma, from action potentials to very slow conductances. 2
• The precise contribution of a given cell depends on geometric factors including cell morphology and the anatomical distribution of active conductances and synaptic inputs. 2

Open vs. Closed Field Configurations

• Pyramidal neurons (the most numerous neurons in hippocampus and cortex) have extended dendritic arbors creating "open fields" where positive and negative sources are spatially separated, generating relatively large signals even with small underlying source magnitudes. 2
• "Closed fields" occur when microsources are symmetrically distributed in space, causing dipoles to cancel each other and resulting in small signals despite relatively large microsources. 2
• Synaptic inputs onto either basal or apical dendrites that are correlated in time generate the largest extracellular potentials, while evenly distributed synaptic inputs cause transmembrane currents to cancel, producing small extracellular potentials. 2

Sensory Neuron Specialization

Nociceptor Function

• Nociceptors are receptors necessary for pain perception that generate action potentials in response to thermal, mechanical, chemical, or polymodal stimuli. 2
• During homeostasis, sensory neurons detect various stimuli to generate physiological pain responses, protecting tissues from acute injuries. 2
• Tissue damage and inflammation result in peripheral axonal injuries and release of pro-inflammatory mediators, potentially causing increased sensitivity of peripheral nerves (peripheral sensitization) and eventually central sensitization where central neurons become highly responsive with heightened pain awareness. 2

Clinical Implications

• Understanding nerve fiber types is fundamental for pain management and understanding reflexes such as coughing. 5
• In predominantly motor neuropathies, reduction in compound muscle action potential (CMAP) amplitude is observed in EMG, correlating with axonal damage. 5