Hypoxia activates BK and Kv channels in rat carotid body glomus cells

Abstract

Inhibition of BK and/or Kv has been proposed to be involved in hypoxia‐induced depolarization and subsequent elevation of intracellular [Ca2+] in carotid body glomus cells. However, depolarization and/or elevation of [Ca2+] are well known to activate BK and Kv, which would oppose glomus cell excitation. First we studied the effect of hypoxia on BK in cell‐attached patches, where the cell Em and intracellular [Ca2+] were allowed to change naturally in response to hypoxia. In cell‐attached patches (140 mM KCl in the pipette and 5 mM in the bath), hypoxia reversibly activated BK while causing inhibition of TASK. In cells partially depolarized by elevating extracellular [KCl] from 5 mM to 12–15 mM KCl, hypoxia also activated BK reversibly. In inside‐out patches showing different levels of BK activity, hypoxia produced no significant effect on BK. Kv could not be detected clearly in cell‐attached patches. Therefore, the role of Kv was tested indirectly by studying the effect of guangxitoxin (GxTX: Kv2 blocker) on hypoxia‐induced rise in intracellular [Ca2+]. GxTX inhibited the outward K+ current by ~50%, and enhanced the hypoxia‐induced elevation of intracellular [Ca2+] 2.3 fold, indicating that hypoxia activated Kv2. These results show that hypoxia activates BK and Kv in rat glomus cells, which helps to limit the hypoxia‐induced excitation of glomus cells.Support or Funding InformationSupported by NIH