Stimulatory regulation of the large-conductance, calcium-activated potassium channel by G proteins in bovine adrenal chromaffin cells
| Autor: | K B, Walsh, S P, Wilson, K J, Long, S C, Lemon |
|---|---|
| Rok vydání: | 1996 |
| Předmět: |
Patch-Clamp Techniques
Potassium Channels Time Factors Cell Membrane Fluorides Kinetics Potassium Channels Calcium-Activated Adrenal Medulla GTP-Binding Proteins Guanosine 5'-O-(3-Thiotriphosphate) Animals Homeostasis Calcium Cattle Large-Conductance Calcium-Activated Potassium Channels Virulence Factors Bordetella Aluminum Compounds Ion Channel Gating Cells Cultured |
| Zdroj: | Molecular pharmacology. 49(2) |
| ISSN: | 0026-895X |
| Popis: | 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 a4-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. |
| Databáze: | OpenAIRE |
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