Severe Hypoxia Activates BK channel in Rat Carotid Body Glomus Cells

Abstract

Large-conductance Ca2+-activated K+ channel (BK) is highly expressed in rat carotid body glomus cells. Previous studies have reported that hypoxia inhibits BK, but the effect of hypoxia in intact glomus cells is not well defined. As hypoxia depolarizes glomus cells and elevates intracellular [Ca2+], we tested the hypothesis that hypoxia activates BK in intact cells. In cell-attached patches with 140 mM KCl in the pipette and 5 mM KCl in the bath solution, BK was always in the closed state, and hypoxia (0% O2) activated BK in ~10% of patches tested. In cell-attached patches, bath application of 1 mM NaCN also activated BK in some patches. When BK was first activated by depolarizing the patch membrane by changing the pipette potential or by perfusing the cells with high KCl (10-15 mM), hypoxia increased the BK activity reversibly. The stimulatory effect of hypoxia on BK was also observed in cell-attached patches with 5 mM KCl in the pipette, if the patch membrane was depolarized first. Study of the relationship among [Ca2+]i, cell Em and BK activity indicated that BK begins to activate when cell depolarizes ~30 mV and [Ca2+]i increases above ~500 nM (from a basal level of ~100 nM). Thus, severe hypoxia activates BK in glomus cells, and this presumably helps to limit over-excitation.