Direct G protein modulation of Cav2 calcium channels.
The regulation of presynaptic, voltage-gated calcium channels by activation of heptahelical G protein-coupled receptors exerts a crucial influence on presynaptic calcium entry and hence on neurotransmitter release. Receptor activation subjects presynaptic N- and P/Q-type calcium channels to a rapid, membrane-delimited inhibition-mediated by direct, voltage-dependent interactions between G protein betagamma subunits and the channels-and to a slower, voltage-independent modulation involving soluble second messenger molecules. In turn, the direct inhibition of the channels is regulated as a function of many factors, including channel subtype, ancillary calcium channel subunits, and the types of G proteins and G protein regulatory factors involved. Twenty-five years after this mode of physiological regulation was first described, we review the investigations that have led to our current understanding of its molecular mechanisms.
Tedford
H William
HW
Hotchkiss Brain Institute, Department of Physiology and Biophysics, University of Calgary, Calgary, Canada.
Zamponi
Gerald W
GW
D000818:Animals; D015220:Calcium Channels / Q000502:physiology; D020864:Calcium Channels, N-Type / Q000502:physiology*; D019204:GTP-Binding Proteins / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D008954:Models, Biological; D017729:Presynaptic Terminals / Q000502:physiology; D021122:Protein Subunits / Q000378:metabolism / Q000502:physiology; D043562:Receptors, G-Protein-Coupled / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology
D015220:Calcium Channels; D020864:Calcium Channels, N-Type; D021122:Protein Subunits; D043562:Receptors, G-Protein-Coupled; D019204:GTP-Binding Proteins