Suppression of glomus cell K + conductance by 4-aminopyridine is not related to [Ca 2+] i, dopamine release and chemosensory discharge from carotid body

Abstract

The hypothesis that suppression of O 2-sensitive K + current is the initial event in hypoxic chemotransduction in the carotid body glomus cells was tested by using 4-aminopyridine (4-AP), a known suppressant of K + current, on intracellular [Ca 2+] i , dopamine secretion and chemosensory discharge in cat carotid body (CB). In vitro experiments were performed with superfused–perfused cat CBs, measuring chemosensory discharge, monitoring dopamine release by microsensors without and with 4-AP (0.2, 1.0 and 2.0 mM in CO 2-HCO 3 - buffer) and recording [Ca 2+] i by ratio fluorometry in isolated cat and rat glomus cells. 4-AP decreased the chemosensory activities in normoxia but remained the same in hypoxia and in flow interruption. It decreased the tissue dopamine release in normoxia, and showed an additional inhibition with hypoxia. Also, 4-AP did not evoke any rise in [Ca 2+] i in glomus cells either during normoxia and hypoxia, although hypoxia stimulated it. Thus, the lack of stimulatory effect on chemosensory discharge, inhibition of dopamine release and unaltered [Ca 2+] i by 4-AP are not consistent with the implied meaning of the suppressant effect on K + current of glomus cells.