[Functional guanine nucleotide-binding proteins in receptor-mediated modulation of voltage-dependent ion channels]

G-proteins act as transducers between cell surface receptors activated by extracellular signals and enzymatic effectors which control the concentrations of cytosolic signal molecules such as cAMP, cGMP, inositol phosphates and calcium. The receptor/G-protein-induced changes of the intracellular concentration of such signal molecules correlates with activity changes of various voltage-dependent ion channels. In some instances, cytosolic signal molecules appear to interact directly with ion channels, thereby causing an alteration of ion channel activity. In other instances, signal molecules affect the function of ion channels by activating protein kinases which, in turn, phosphorylate either proteins constituting extracellular signal- and voltage-dependent ion channels or non-identified membranous regulatory components. Recent findings suggest a third, membrane-confined mechanism which does not involve cytosolic signal molecules but a close control of voltage-dependent ion channels by G-proteins. Ion channels that are modulated by extracellular signals according to this newly discovered principle include those for calcium and potassium in neuronal, cardiac and endocrine cells. G-proteins involved in the hormonal stimulation of potassium and calcium channels belong to the family of Gi-type G-proteins which are functionally uncoupled from activating receptors by pertussis toxin. In addition, the cholera toxin-sensitive G-protein, Gs, may directly stimulate cardiac calcium channels. Hormonal inhibition of calcium channels is possibly mediated by Go which, like G-proteins of the Gi-family, is functionally impaired by pertussis toxin.(ABSTRACT TRUNCATED AT 250 WORDS)