TASK-like potassium channels and oxygen sensing in the carotid body.
Chemosensing by type-1 cells of the carotid body involves a series of events which culminate in the calcium-dependent secretion of neurotransmitter substances which then excite afferent nerves. This response is mediated via membrane depolarisation and voltage-gated calcium entry. Studies utilising isolated cells indicates that the membrane depolarisation in response to hypoxia, and acidosis, appears to be primarily mediated via the inhibition of a background K(+)-current. The pharmacological and biophysical characteristics of these channels suggest that they are probably closely related to the TASK subfamily of tandem-P-domain K(+)-channels. Indeed they show greatest similarity to TASK-1 and -3. In addition to being sensitive to hypoxia and acidosis, the background K(+)-channels of the type-1 cell are also remarkably sensitive to inhibition of mitochondrial energy metabolism. Metabolic poisons are known potent stimulants of the carotid body and cause membrane depolarisation of type-1 cells. In the presence of metabolic inhibitors hypoxic sensitivity is lost suggesting that oxygen sensing may itself be mediated via depression of mitochondrial energy production. Thus these TASK-like background channels play a central role in mediating the chemotransduction of several different stimuli within the type-1 cell. The mechanisms by which metabolic/oxygen sensitivity might be conferred upon these channels are briefly discussed.
Buckler
Keith J
KJ
Department of Physiology Anatomy and Genetics, Sherrington Building, Parks Road, Oxford, UK. keith.buckler@dpag.ox.ac.uk
D000818:Animals; D002344:Carotid Body / Q000502:physiology*; D002628:Chemoreceptor Cells / Q000502:physiology*; D006801:Humans; D040542:Mechanotransduction, Cellular / Q000502:physiology*; D008928:Mitochondria / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D024683:Potassium Channels, Tandem Pore Domain / Q000378:metabolism*
D009419:Nerve Tissue Proteins; D024683:Potassium Channels, Tandem Pore Domain; C420132:potassium channel subfamily K member 3