Are oxygen dependent K + channels essential for carotid body chemo-transduction?

Abstract

The mechanism by which the carotid body senses hypoxia and causes an increase in spiking activity on the sinus nerve is not well resolved. Most experimental attention is focused on the glomus cell, a secretory cell which is apposed to the afferent nerve endings and which is the presumed site of oxygen sensing. It is proposed that hypoxia causes glomus cell depolarization by inhibiting an oxygen-sensitive K + current. This leads to depolarization, activation of voltage-gated calcium influx and enhanced secretion of an excitatory transmitter. At present, 4 candidate oxygen-sensitive K + currents have been identified based on patch-clamp studies of isolated glomus cells. Recent experiments using intact carotid bodies have been undertaken to identify which current is most likely to mediate the hypoxia response. Three of the four currents are sensitive to K + channel blocking agents (TEA, 4-AP and charybdotoxin), yet all these agents failed to mimic hypoxia, neither stimulating chemoreceptor nerve activity nor enhancing catecholamine secretion. Thus, the fourth current, a leak current which is insensitive to these agents is the most likely candidate for mediating glomus cell depolarization, but the drug-sensitivity of this current is not yet known which precludes a direct test of this speculation.