Regulation of a TASK-like Potassium Channel in Rat Carotid Body Type I Cells by ATP
The carotid body plays a central role in initiating cardiovascular and respiratory responses to hypoxia. Previous work from this laboratory has demonstrated that hypoxia inhibits TASK-like K+ -channels in isolated neonatal rat carotid body type I cells (Buckler et al., 2000). The consequent reduction in background K+-current leads to type-1 cell membrane depolarisation (Buckler, 1997), voltage-gated calcium entry and thus excitation of the carotid body. The mechanisms by which hypoxia modulates these K+ channels is still unknown, however the effects of hypoxia are mimicked by a wide range of inhibitors of oxidative phosphorylation. Uncouplers, electron transport inhibitors (e.g. cyanide, rotenone & myxothiazol) and inhibitors of ATP synthase (oligomycin) are all potent stimulants of the carotid body (Anichkov & Belen‘kii, 1963; Gonzalez et al., 1994) and potent inhibitors of background K+-current (Wyatt & Buckler, 2004). Moreover background K+-current sensitivity to hypoxia is lost in the presence of metabolic inhibitors (Wyatt & Buckler, 2004) suggesting that ATP synthesis may be a prerequisite for the expression of oxygen sensitivity. Further support for the idea that background K+-channel activity may be dependent upon cellular ATP levels comes from the observation that following patch excision (from the cell attached to the inside out configuration) there is an abrupt rundown of background K+-channel activity which can be partially reversed by the addition of mM levels of ATP to the intracellular solution (Williams & Buckler, 2004). In this study we have further investigated the action of ATP on background K+-channels in order to evaluate the potential role for ATP in modulating channel activity and to identify general mechanisms by which ATP might act.
KeywordsChannel Activity Carotid Body Single Channel Recording Dose Dependent Activation Single Channel Activity
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- Anichkov SV & Belen kii ML (1963) Pharmacology of the carotid body chemoreceptors. Macmillan Publishing, New YorkGoogle Scholar
- Buckler KJ (1997) A novel oxygen sensitive potassium current in rat carotid body type-I cells. J Physiol 498.3: 649–662.Google Scholar
- Wyatt CN & Buckler KJ (2004) The effect of mitochondrial inhibitors on membrane currents in isolated neonatal rat carotid body type I cells. J Physiol 556.1: 175–191.Google Scholar