Ca2+-dependent modulation of voltage-gated Ca2+ channels.
BACKGROUND
Voltage-gated (Cav) Ca2+ channels are multi-subunit complexes that play diverse roles in a wide variety of tissues. A fundamental mechanism controlling Cav channel function involves the Ca2+ ions that permeate the channel pore. Ca2+ influx through Cav channels mediates feedback regulation to the channel that is both negative (Ca2+-dependent inactivation, CDI) and positive (Ca2+-dependent facilitation, CDF).


METHODS
This review highlights general mechanisms of CDI and CDF with an emphasis on how these processes have been studied electrophysiologically in native and heterologous expression systems.


CONCLUSIONS
Electrophysiological analyses have led to detailed insights into the mechanisms and prevalence of CDI and CDF as Cav channel regulatory mechanisms. All Cav channel family members undergo some form of Ca2+-dependent feedback that relies on CaM or a related Ca2+ binding protein. Tremendous progress has been made in characterizing the role of CaM in CDI and CDF. Yet, what contributes to the heterogeneity of CDI/CDF in various cell-types and how Ca2+-dependent regulation of Cav channels controls Ca2+ signaling remain largely unexplored.


CONCLUSIONS
Ca2+ influx through Cav channels regulates diverse physiological events including excitation-contraction coupling in muscle, neurotransmitter and hormone release, and Ca2+-dependent gene transcription. Therefore, the mechanisms that regulate channels, such as CDI and CDF, can have a large impact on the signaling potential of excitable cells in various physiological contexts. This article is part of a Special Issue entitled Biochemical, biophysical and genetic approaches to intracellular calcium signaling.
Department of Molecular Physiology and Biophysics, University of Iowa, Iowa City, IA 52242, USA.
Carl
C
Christel
Amy
A
Lee
D000818:Animals; D002118:Calcium / Q000502:physiology*; D015220:Calcium Channels / Q000378:metabolism / Q000502:physiology*; D020013:Calcium Signaling; D002135:Calcium-Binding Proteins / Q000378:metabolism; D025461:Feedback, Physiological; D006801:Humans; D008564:Membrane Potentials; D009474:Neurons / Q000378:metabolism / Q000502:physiology; D009928:Organ Specificity; D020033:Protein Isoforms / Q000378:metabolism / Q000502:physiology; D021122:Protein Subunits / Q000378:metabolism / Q000502:physiology
D015220:Calcium Channels; D002135:Calcium-Binding Proteins; D020033:Protein Isoforms; D021122:Protein Subunits; D002118:Calcium