Fig. 3.

Halogenated volatile anesthetics inhibit adenosine triphosphate–sensitive K⁺ (K_ATP) channels. (A) Whole cell recording at a holding potential of −20 mV from an HEK293 cell transfected with Kir6.2 and SUR1. The dashed line indicates the zero-current level. Halothane, isoflurane, and sevoflurane (1 mm each) were bath applied as indicated by the horizontal bars. Each drug reversibly inhibited the whole cell K_ATP current. (B) Current–voltage relations taken from a recording as that shown in A demonstrating that the current inhibited by the volatile anesthetics has a reversal potential near E_K. (C) Concentration–response curves of the inhibitory effect of halothane (n = 4–8), isoflurane (n = 3–5), and sevoflurane (n = 3–8) on whole cell K_ATP currents. The current in presence of the drug (I) is expressed as a fraction of the current in its absence (I_C). The solid lines describe the best fit with a Hill equation using K_i = 1.32 mm and Hill coefficient (h) = 1.75 for halothane, K_i = 2.08 mm and h = 1.39 for isoflurane, and K_i = 47 mm and h = 0.34 for sevoflurane. In each case, it is assumed that complete inhibition of the K_ATP current could theoretically be achieved with high enough concentrations of the anesthetic. One minimum alveolar concentration is indicated by the vertical dashed line in each graph.