title: GABA(B) receptor activation augments TASK-1 in MAH cells and mediates autoreceptor feedback during hypoxia.
abstract: 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 microM 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 microM Zn(2+), a selective inhibitor of TASK-1. When recording membrane potential from MAH cells in clusters, hypoxic depolarisation was augmented by 100 nM 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.
authors.affiliation: Department of Biology, McMaster University, 1280 Main St West, Hamilton, Ont, Canada L8S 4K1.
authors.forename: Rosalyn P
authors.initials: RP
authors.lastname: Johnson
authors.forename: Ian M
authors.initials: IM
authors.lastname: Fearon
mesh_terms: D000222:Adaptation, Physiological; D000313:Adrenal Medulla / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D017660:Autoreceptors / Q000378:metabolism; D001418:Baclofen / Q000494:pharmacology*; D015687:Cell Hypoxia / Q000502:physiology; D002460:Cell Line; D019439:Chromaffin Cells / Q000187:drug effects / Q000502:physiology*; D005246:Feedback; D058788:GABA-B Receptor Antagonists; D006706:Homeostasis; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology; D008564:Membrane Potentials / Q000187:drug effects; D009419:Nerve Tissue Proteins / Q000819:agonists / Q000378:metabolism*; D010721:Phosphinic Acids / Q000494:pharmacology; D015221:Potassium Channels / Q000819:agonists / Q000378:metabolism*; D024683:Potassium Channels, Tandem Pore Domain; D011412:Propanolamines / Q000494:pharmacology; D051381:Rats; D018080:Receptors, GABA-B / Q000378:metabolism*; D015032:Zinc / Q000494:pharmacology
chemical_list: D017660:Autoreceptors; D058788:GABA-B Receptor Antagonists; D009419:Nerve Tissue Proteins; D010721:Phosphinic Acids; D015221:Potassium Channels; D024683:Potassium Channels, Tandem Pore Domain; D011412:Propanolamines; D018080:Receptors, GABA-B; C085075:CGP 55845A; C420132:potassium channel subfamily K member 3; D001418:Baclofen; D015032:Zinc