RT Journal Article SR Electronic T1 Direct G Protein Modulation of Cav2 Calcium Channels JF Pharmacological Reviews JO Pharmacol Rev FD American Society for Pharmacology and Experimental Therapeutics SP 837 OP 862 DO 10.1124/pr.58.4.11 VO 58 IS 4 A1 H. William Tedford A1 Gerald W. Zamponi YR 2006 UL http://pharmrev.aspetjournals.org/content/58/4/837.abstract AB 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.