TY - JOUR T1 - Direct G Protein Modulation of Ca<sub>v</sub>2 Calcium Channels JF - Pharmacological Reviews JO - Pharmacol Rev SP - 837 LP - 862 DO - 10.1124/pr.58.4.11 VL - 58 IS - 4 AU - H. William Tedford AU - Gerald W. Zamponi Y1 - 2006/12/01 UR - http://pharmrev.aspetjournals.org/content/58/4/837.abstract N2 - 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 βγ 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. ER -