A key role for the subunit SUR2B in the preferential activation of vascular K ATP channels by isoflurane

Abstract

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 μM 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. © 2006 Nature Publishing Group. All rights reserved.