K + currents of glomus cells and chemosensory functions of carotid body

Abstract

The mechanism by which the carotid body senses hypoxia is not resolved, but the glomus cell, a secretory cell apposed to the afferent nerve endings, is believed to play an essential role. It is proposed that hypoxia causes glomus cell depolarization, leading to activation of voltage-gated calcium influx and enhanced secretion of an excitatory transmitter. The initial step, hypoxia induced depolarization, may be mediated by several candidate K + channels which are sensitive to hypoxia, including: (1) a transient, voltage-dependent current; (2) a calcium and voltage dependent current; and (3) a non-voltage dependent, leak K + current. If these channels represent the initial step in the hypoxia transduction cascade then it would be expected that K + channel blocking agents would mimic the hypoxia response, leading to glomus cell secretion and increased nerve activity. This has been tested for the first two channels which are sensitive to classical K + channel blocking agents, and, in general, results have not borne out this prediction. At present, the pharmacology of the leak K + channel is not determined, and the experiment has not been undertaken. Thus, at present, hypoxic inhibition to a K + channel in the glomus cell may initiate chemotransduction but there are many unanswered questions, especially the failure of K + channel blocking agents to emulate the hypoxic response.