GABAB 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 GABAB receptor-mediated activation of the background K+ channel TASK-1. Here, we examined the effects of the selective GABAB 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, 50μM baclofen enhanced a K+ current which was linear and reversed close to 0mV. Under physiological K + conditions, baclofen enhanced outward K+ current and caused membrane hyperpolarisation, effects inhibited by 100nM CGP 55845. Current enhancement was virtually abolished in the presence of 300μM Zn 2+, 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 GABAB receptors mediate autoreceptor feedback in the adrenal medulla presumably via TASK-1, demonstrating a common autoregulatory feedback pathway in neurosecretory, chemosensitive cells. © 2003 Elsevier Inc. All rights reserved.