Biochemical and Biophysical Research Communications, Vol.312, No.2, 421-425, 2003
GABA(B) receptor activation augments TASK-1 in MAH cells and mediates autoreceptor feedback during hypoxia
Previously, we demonstrated an autoregulatory feedback loop in the rat carotid body (CB), involving presynaptic GABA(B) receptor-mediated activation of the background K+ channel TASK-1. Here, we examined the effects of the selective GABA(B) receptor agonist baclofen on K+ currents in immortalised adrenomedullary chromaffin (MAH) cells, which share the same sympathoadrenal lineage as CB type I cells. Under symmetrical K+ conditions, 50 muM baclofen enhanced a K+ current which was linear and reversed close to 0 mV. Under physiological K+ conditions, baclofen enhanced outward K+ current and caused membrane hyperpolarisation, effects inhibited by 100 nM CGP 55845. Current enhancement was virtually abolished in the presence of 300 muM Zn2+, a selective inhibitor of TASK-1. When recording membrane potential from MAH cells in clusters, hypoxic depolarisation was augmented by 100nM CGP 55845. These data demonstrate that GABA(B) receptors mediate autoreceptor feedback in the adrenal medulla presumably via TASK-1, demonstrating a common autoregulatory feedback pathway in neurosecretory, chemosensitive cells. (C) 2003 Elsevier Inc. All rights reserved.