Biophysical properties of the membrane influence spike initiation dynamics and neuronal excitability: a focus on Kv1 channels in myelinated axons.

Neurons and their subcellular compartments exhibit distinct forms of excitability. In 1948, Alan Hodgkin described different classes of neuronal excitability, each characterized by unique spiking responses to a constant stimulus. Despite these early insights, the mechanisms by which membrane properties influence spike initiation and excitability remain poorly understood. This review explores the nonlinear dynamics underlying spike initiation across excitability classes, emphasizing how these differences contribute to the neural encoding and processing of diverse information. Within a single neuron, compartments such as the soma, axon initial segment (AIS), and axon can exhibit functionally distinct excitability profiles due to differences in ion channel expression and membrane properties. For instance, the biophysical properties of myelinated axons, particularly the expression and distribution of voltage-gated potassium (Kv1) channels, play a key role in maintaining the directional fidelity of action potential propagation by facilitating orthodromic transmission and suppressing antidromic activity. These compartment-specific dynamics underscore the intricate design of neural systems to maintain the precision and efficiency of neural signalling. Moreover, perturbations in excitability are implicated in various neurological disorders, including epilepsy and chronic pain, highlighting the importance of maintaining physiological excitability profiles. By exploring these mechanisms, this review aims to provide insight into how alterations in membrane biophysics may inform future therapeutic strategies targeting excitability-related pathologies.