A key role for the subunit SUR2B in the preferential activation of vascular K(ATP) channels by isoflurane.
Background and purpose:It has been postulated that isoflurane, a volatile anaesthetic, produces vasodilatation through activation of ATP-sensitive K(+) (K(ATP)) channels. However, there is no direct evidence for the activation of vascular K(ATP) channels by isoflurane. This study was conducted to examine the effect of isoflurane on vascular K(ATP) channels and compare it with that on cardiac K(ATP) channels.Experimental approach:Effects of isoflurane on K(ATP) channels were examined in aortic smooth muscle cells and cardiomyocytes of the mouse using patch clamp techniques. Effects of the anaesthetic on the K(ATP) channels with different combinations of the inward rectifier pore subunits ( Kir6.1 and Kir6.2) and sulphonylurea receptor subunits (SUR2A and SUR2B) reconstituted in a heterologous expression system were also examined.Key results:Isoflurane increased the coronary flow in Langendorff-perfused mouse hearts in a concentration-dependent manner, which was abolished by 10 muM glibenclamide. In enzymically-dissociated aortic smooth muscle cells, isoflurane evoked a glibenclamide-sensitive current (i.e. K(ATP) current). In isolated mouse ventricular cells, however, isoflurane failed to evoke the K(ATP) current unless the K(ATP) current was preactivated by the K(+) channel opener pinacidil. Although isoflurane readily activated the Kir6.1/SUR2B channels (vascular type), the volatile anesthetic could not activate the Kir6.2/SUR2A channels (cardiac type) expressed in HEK293 cells. Isoflurane activated a glibenclamide-sensitive current in HEK293 cells expressing Kir6.2/SUR2B channels.Conclusion and implications:Isoflurane activates K(ATP) channels in vascular smooth muscle cells and produces coronary vasodilation in mouse hearts. SUR2B may be important for the activation of vascular-type K(ATP) channels by isoflurane.British Journal of Pharmacology (2006) 149, 573-580. doi:10.1038/sj.bjp.0706891; published online 25 September 2006.[1]References
- A key role for the subunit SUR2B in the preferential activation of vascular K(ATP) channels by isoflurane. Fujita, H., Ogura, T., Tamagawa, M., Uemura, H., Sato, T., Ishida, A., Imamaki, M., Kimura, F., Miyazaki, M., Nakaya, H. Br. J. Pharmacol. (2006) [Pubmed]
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