Dexmedetomidine directly inhibits vascular ATP-sensitive potassium channels

Aims: Dexmedetomidine is reported to have an effect on peripheral vasoconstriction; however, the exact mechanisms underlying this process are unclear. In this study, we hypothesized that dexmedetomidine-induced inhibition of vascular ATP-sensitive K+ (K-ATP) channels may be associated with this vasoconstriction. To test this hypothesis, we investigated the effects of dexmedetomidine on vascular K-ATP-channel activity at the single-channel level. Main methods: We used cell-attached and inside-out patch-clamp configurations to examine the effects of dexmedetomidine on the activities of native rat vascular K-ATP channels, recombinant}cap channels with different combinations of various inwardly rectifying potassium channels (Kir6.0 family: Kir6.1, 6.2) and sulfonylurea receptor subunits (SUR1, 2A, 2B), and SUR-deficient channels derived from a truncated isoform of Kir6.2 subunit, namely, Kir6.2 Delta C36 channels. Key findings: Dexmedetomidine was observed to inhibit the native rat vascular K-ATP channels in both cell-attached and inside-out configurations. This drug also inhibited the activity of all types of recombinant SUR/Kir6.0 K-ATP channels as well as Kir6.2,Delta 36 channels with equivalent potency. Significance: These results indicate that dexmedetomidine directly inhibits K-ATP channels through the Kir6.0 subunit. (C) 2011 Elsevier Inc. All rights reserved.