Stimulatory regulation of the large-conductance, calcium-activated potassium channel by G proteins in bovine adrenal chromaffin cells

KB Walsh, SP Wilson, KJ Long and SC Lemon

Department of Pharmacology, University of South Carolina, School of Medicine, Columbia 29208, USA.

G proteins regulate the electrical activity of various cells through their actions on membrane ion channels. In the present study, the effect of G proteins was examined on unitary, large conductance (BK), Ca(2+)-activated K+ channels measured in excised, inside-out patches of membrane obtained from cultured bovine adrenal chromaffin cells. Cytoplasmic application of either guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S) or AlF-4 to stimulate G proteins resulted in a > 4-fold increase in the open probability of the BK channel measured at +40 mV in the presence of a 1 microM concentration of Ca2+. A similar stimulatory regulation was observed after the addition of an activated, mixed Gi/Go alpha preparation. The increase in the open probability during G protein stimulation was associated with a large reduction in the duration of a long closed state of the channel and could be observed in the presence of a protein kinase inhibitor. The half- maximal voltage required for steady state activation of the BK channel decreased from +63 mV to +48 mV in the presence of GTP gamma S. In addition, the half-maximal Ca2+ concentration required for channel opening was reduced from 11.7 microM in control measurements to 1.3 microM during regulation by GTP gamma S. Thus, G proteins increase the open probability of the chromaffin BK Ca(2+)-activated K+ channel by shifting the voltage dependence of channel gating to more negative potentials and by enhancing the affinity of the channel for Ca2+. Stimulatory regulation may provide a compensatory mechanism for decreasing the action potential duration during secretagogue-mediated exocytosis.

Volume 49, Issue 2, pp. 379-386, 02/01/1996
Copyright © 1996 by American Society for Pharmacology and Experimental Therapeutics

This article has been cited by other articles:

				P.-Y. Deng and S. Lei Bidirectional modulation of GABAergic transmission by cholecystokinin in hippocampal dentate gyrus granule cells of juvenile rats J. Physiol., April 15, 2006; 572(2): 425 - 442. [Abstract] [Full Text] [PDF]