Control of voltage-dependent Ca2+ channels by G protein-coupled receptors.
G proteins act as transducers between membrane receptors activated by extracellular signals and enzymatic effectors controlling the concentration of cytosolic signal molecules such as cAMP, cGMP, inositol phosphates and Ca2+. In some instances, the receptor/G protein-induced changes in the concentration of cytosolic signal molecules correlate with activity changes of voltage-dependent Ca2+ channels. Ca2+ channel modulation, in these cases, requires the participation of protein kinases whose activity is stimulated by cytosolic signal molecules. The respective protein kinases phosphorylate Ca2+ channel-forming proteins or unknown regulatory components. More recent findings suggest another membrane-confined mechanism that does not involve cytosolic signal molecules but rather a more direct control of voltage-dependent Ca2+ channels by G proteins. Modulation of Ca2+ channel activity that follows this apparently membrane-confined mechanism has been described to occur in neuronal, cardiac, and endocrine cells. The G protein involved in the hormonal stimulation of Ca2+ channels in endocrine cells may belong to the family of Gi-type G proteins, which are functionally uncoupled from activating receptors by pertussis toxin. The G protein Gs, which is activated by cholera toxin, may stimulate cardiac Ca2+ channels without the involvement of a cAMP-dependent intermediate step. Hormonal inhibition of Ca2+ channels in neuronal and endocrine cells is mediated by a pertussis toxin-sensitive G protein, possibly Go. Whether G proteins act by binding directly to Ca2+ channels or through interaction with as yet undetermined regulatory components of the plasma membrane remains to be clarified.
Rosenthal
W
W
Institute for Pharacology, Free University of Berlin, Federal Republic of Germany.
Hescheler
J
J
Trautwein
W
W
Schultz
G
G
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000502:physiology; D004594:Electrophysiology; D019204:GTP-Binding Proteins / Q000378:metabolism* / Q000502:physiology; D007473:Ion Channels / Q000502:physiology*; D011956:Receptors, Cell Surface / Q000378:metabolism / Q000502:physiology*; D013268:Stimulation, Chemical
D002121:Calcium Channel Blockers; D007473:Ion Channels; D011956:Receptors, Cell Surface; D019204:GTP-Binding Proteins; D002118:Calcium