Signaling by Ion Channels: Pathways, Dynamics and Channelopathies

Abstract

Charged ions and ion channels play a critical role in regulating the electrical activities of excitable cells. This review discusses the principles of ion channel regulation in the time domain, as well as the diseases that can arise from channel dysfunction and disturbances in ionic balance. Ion channel signaling is a dynamic process that is essential for various physiological functions, including pain sensation, motor control, and the body's response to stress, such as fight-or-flight response.

Figure 1

Simulated action potentials generated using the Hodgkin-Huxley model. Different amounts of current were applied to stimulate trains of action potentials with varying frequencies. The current stimulus ranged from low to high (5 pA, 10 pA, and 20 pA from top to bottom), and the parameters used were based on action potential of the squid giant axon and obtained from the Handbook of Physiology - the Nervous System, Chapter 4, authored by Bertil Hille (1977).

Figure 2

Schematic cartoon showing the multimodal activation of TRPV1 channels by both heat and capsaicin binding. Membrane lipid PI(4,5)P₂ binds to TRPV1 channels directly.

Figure 3

Fast and slow G protein-dependent signaling pathways for modulating ion channels. Activation of the G_i/o-coupled M2 muscarinic acetylcholine receptors releases the G protein βγ subunits, which activates GIRK channels. On the other hand, activation of the G_q-coupled M1 muscarinic acetylcholine receptors activates PLC, which hydrolyzes membrane lipid PI(4,5)P₂, an essential activator of GIRK channels.