DISRUPTION OF ACTIN CYTOSKELETON ATTENUATES SULFONYLUREA INHIBITION OF CARDIAC ATP-SENSITIVE K+ CHANNELS

Two actin filament-depolymerizing agents, DNase I and cytochalasin D, were used to examine the involvement of the cytoskeleton in the functi onal interaction between the sulfonylurea receptor (SUR) and the ATP-s ensitive K+ (K-ATP) channels. Isolated rat ventricular cardiomyocytes were studied using open cell-attached patches for single-channel recor ding. Bath application of DNase I (100 mu ug/ml) or cytochalasin D (10 mu M) stimulated the K-ATP channel activities (in presence of 30 mu M ATP), and these channels became resistant to inhibition by tolbutamid e (0.5 mM). After exposure to tolbutamide, the relative NP0 value was 0.09 +/- 0.02 in control patches in absence of actin disrupters, and 0 .67 +/- 0.22 or 0.65 +/- 0.10*, respectively, in cells treated with D Nase I or cytochalasine D (P < 0.05 vs, control). The inhibitory acti on of glibenclamide (10 mu M) on the K-ATP channels was also attenuate d by DNase I, Thus, the disruption of the actin cytoskeleton attenuate s the ability of SUR to inhibit the opening of K-ATP channels.