Regulation of sodium and calcium channels by signaling complexes.
Membrane depolarization and intracellular calcium transients generated by activation of voltage-gated sodium and calcium channels are local signals, which initiate physiological processes such as action potential conduction, synaptic transmission, and excitation-contraction coupling. Targeting of effector proteins and regulatory proteins to ion channels is an important mechanism to ensure speed, specificity, and precise regulation of signaling events in response to local stimuli. In this article, we review recent experimental results showing that sodium and calcium channels form local signaling complexes, in which effector proteins, anchoring proteins, and regulatory proteins interact directly with ion channels. The intracellular domains of these channels serve as signaling platforms, mediating their participation in intracellular signaling processes. These protein-protein interactions are important for efficient synaptic transmission and for regulation of ion channels by neurotransmitters and intracellular second messengers. These localized signaling complexes are essential for normal function and regulation of electrical excitability, synaptic transmission, and excitation-contraction coupling.
Catterall
William A
WA
Department of Pharmacology, University of Washington, Seattle, Washington 98195-7280, USA. wcatt@u.washington.edu
Hulme
Joanne T
JT
Jiang
Xin
X
Few
W Preston
WP
D000818:Animals; D015220:Calcium Channels / Q000502:physiology*; D004594:Electrophysiology; D025461:Feedback, Physiological / Q000502:physiology*; D006801:Humans; D046912:Multiprotein Complexes / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*; D015222:Sodium Channels / Q000502:physiology*
D015220:Calcium Channels; D046912:Multiprotein Complexes; D015222:Sodium Channels