Activation of voltage-dependent K+ channels strongly limits hypoxia-induced elevation of [Ca2+]i in rat carotid body glomus cells

Abstract

Large-conductance K_Ca (BK) and other voltage-dependent K⁺ channels (Kv) are highly expressed in carotid body (CB) glomus cells, but their role in hypoxia-induced excitation is still not well defined and remains controversial. We addressed this issue by studying the effects of inhibitors of BK (IBTX) and BK/Kv (TEA/4-AP) on [Ca²⁺]_i responses to a wide range of hypoxia at different levels of resting cell Em. IBTX and TEA/4-AP did not affect the basal [Ca²⁺]_i in isolated glomus cells bathed in 5 mm KCl_o, but elicited transient increases in [Ca²⁺]_i in cells that were moderately depolarized (11–20 mV) by elevation of [KCl]_o (12–20 mm). Thus, BK and Kv were mostly closed at rest and activated by depolarization. Four different levels of hypoxia (mild, moderate, severe, and anoxia) were used to produce a wide range of [Ca²⁺]_i elevation (0-700 nm). IBTX did not affect the rise in [Ca²⁺]_i, but TEA/4-AP strongly (∼3-fold) enhanced [Ca²⁺]_i rise by moderate and severe levels of hypoxia. Guangxitoxin, a Kv2 blocker, inhibited the whole-cell current by ∼50%, and enhanced 2-fold the [Ca²⁺]_i rise elicited by moderate and severe levels of hypoxia. Anoxia did not directly affect BK, but activated BK via depolarization. Our findings do not support the view that hypoxia inhibits BK/Kv to initiate or maintain the hypoxic response. Rather, our results show that BK/Kv are activated as glomus cells depolarize in response to hypoxia, which then limits the rise in [Ca²⁺]_i. Inhibition of Kv may provide a mechanism to enhance the chemosensory activity of the CB and ventilation.

This article is protected by copyright. All rights reserved

from Physiology via xlomafota13 on Inoreader http://ift.tt/2zSRwEZ
via IFTTT