Muscarinic modulation of TASK-like background potassium channel in rat carotid body chemoreceptor cells

Abstract: 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 Ca2+ 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 (100µM) or muscarine (50µM) increased intracellular Ca2+ levels. In cell-attached patch recordings, TASK-K+ background channel activity was reduced by ∼50% during mAChR activation and by the diacylglycerol analogue oleoylacetylglycerol (OAG, 20µM). 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 (50µM) 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. [Copyright &y& Elsevier]