Voltage-dependent potassium (K⁺) channel-mediated effects of isoflurane on vascular smooth muscle (VSM) transmembrane potential

Volatile anesthetics vasodilate and this effect is associated with a hyperpolarization of the VSM. The K⁺ channel is the principle determinant of the VSM E_m. Previously, we observed that blockade of K_Ca channels inhibited the hyperpolarization of mesenteric arterial and venous VSM produced by I MAC inhaled isoflurane. The objective of the current study was to investigate the effects of isoflurane on K_v channels in the VSM. Small (200-300 μM) mesenteric arteries and veins were externalized and superfused with physiologic salt solution (PSS) in a temperature-regulated chamber. After local chemical denervation with 6 hydroxydopamine (in the PSS), we measured the effects of isoflurane on in situ single cell VSM E_m with blockade of K_v channels using 3 mM 4-aminopyridinc in the following two protocols: 1). pre, 4AP, 4AP + ISO, post; 2). pre, ISO, 4AP, 4AP + ISO. In mesenteric arteries, 4AP caused a small depolarization. Its effect on veins was minimal. 4AP had little or no effect on ISO-mediated hyperpolarization in ether protocol 1 (figure) or protocol 2 (not illustrated). While previous data indicated that ISO-mediated hyperpolarization of VSM involved enhanced (or maintained) opening of K_Ca channels, the current results suggest that K_v channel opening does not mediate these effects in the in situ condition.