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Titolo:
STIMULATORY REGULATION OF THE LARGE-CONDUCTANCE, CALCIUM-ACTIVATED POTASSIUM CHANNEL BY G-PROTEINS IN BOVINE ADRENAL CHROMAFFIN CELLS
Autore:
WALSH KB; WILSON SP; LONG KJ; LEMON SC;
Indirizzi:
UNIV S CAROLINA,SCH MED,DEPT PHARMACOL COLUMBIA SC 29208
Titolo Testata:
Molecular pharmacology
fascicolo: 2, volume: 49, anno: 1996,
pagine: 379 - 386
SICI:
0026-895X(1996)49:2<379:SROTLC>2.0.ZU;2-K
Fonte:
ISI
Lingua:
ENG
Soggetto:
CA-2+-ACTIVATED K+ CHANNELS; LIPID BILAYERS; KINASE-A; MODULATION; CURRENTS; BLOCKADE; PHOSPHORYLATION; INHIBITION; MEMBRANES; COMPONENT;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
40
Recensione:
Indirizzi per estratti:
Citazione:
K.B. Walsh et al., "STIMULATORY REGULATION OF THE LARGE-CONDUCTANCE, CALCIUM-ACTIVATED POTASSIUM CHANNEL BY G-PROTEINS IN BOVINE ADRENAL CHROMAFFIN CELLS", Molecular pharmacology, 49(2), 1996, pp. 379-386

Abstract

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), Ca2+-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 AlF4- 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 mu M concentration of Ca2+. A similar stimulatory regulation was observed after the addition of an activated, mixed G(i)/G(o alpha) preparation. The increase in the open probability during G protein stimulation was associated with a large reduction in the duration ofa 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 mu M in control measurements to 1.3 mu M during regulation by GTP gammaS. Thus, G proteins increase the open probability of the chromaffin BK Ca2+-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.

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Documento generato il 12/08/20 alle ore 20:14:44