Muscarinic modulation of TASK-like background potassium channel in rat carotid body chemoreceptor cells.
The carotid body is the main peripheral arterial chemoreceptor and it is essential to initiate the cardiovascular and respiratory compensatory reflex responses to a decrease in the arterial oxygen. The carotid body chemoreceptor (type-I) cells respond to hypoxia with membrane depolarization, voltage-gated Ca(2+) entry and secretion of transmitters. A key step in this response is the inhibition of a TASK-like background K(+) current. It has been reported that TASK-K(+) channels can be modulated by G-protein coupled receptors, such as the muscarinic acetylcholine receptor (mAChRs). Since there is a proposed role for ACh as an autocrine/paracrine modulator of the carotid body function, we have investigated the possible regulation of the background K(+) current by mAChRs. In identified type-I cells, methacholine (100microM) or muscarine (50microM) increased intracellular Ca(2+) levels. In cell-attached patch recordings, TASK-K(+) background channel activity was reduced by approximately 50% during mAChR activation and by the diacylglycerol analogue oleoylacetylglycerol (OAG, 20microM). The co-application of both metacholine and OAG do not further inhibit K(+) channel activity. In addition, two chemically different inhibitors of protein kinase C activity, calphostin C (100nM) and chelerythrine (50microM) are both able to suppress the muscarinic inhibition of the TASK-like K(+) channel and to increase channel activity in the absence of mAChR agonists. Our results suggest a muscarinic regulation of the TASK-like K(+) current in rat carotid body type-I cells through a PLC/PKC-dependent pathway. Additionally, our findings are consistent with an autocrine/paracrine role for cholinergic autoreceptors present within the carotid body.
Department of Physiology, Faculty of Biological Sciences, Pontificia Universidad Católica de Chile, Santiago, Chile.
Fernando C
FC
Ortiz
Rodrigo
R
Varas
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002344:Carotid Body / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D018721:Muscarinic Agonists / Q000494:pharmacology; D018727:Muscarinic Antagonists / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D024683:Potassium Channels, Tandem Pore Domain / Q000502:physiology*; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011976:Receptors, Muscarinic / Q000502:physiology*
D018721:Muscarinic Agonists; D018727:Muscarinic Antagonists; D024683:Potassium Channels, Tandem Pore Domain; D011976:Receptors, Muscarinic; D011493:Protein Kinase C; D002118:Calcium