Actin microfilament disrupters enhance K-ATP channel opening in patches from guinea-pig cardiomyocytes

1. To determine whether actin filament networks are associated with the regulation of ATP-sensitive K+ (K-ATP) channel activity, single channel currents were measured in the inside-out configuration, and cytoskeletal disrupters applied to the internal side of patches excised from guinea-pig ventricular myocytes. 2. Treatment of patches with DNase I (10-200 mu g ml(-1)), which forms complexes with G-actin and prevents actin filament formation, antagonized the ATP-induced inhibition of K-ATP channels. 3. In the absence of ATP, DNase I did not increase K-ATP channel activity. 4. When denatured by boiling or co-incubated with purified actin subunits (200 mu g ml(-1)), DNase I (100 mu g ml(-1)) did not antagonize the ATP-induced inhibition of K-ATP channels. 5. The DNase I-induced decrease in the sensitivity of K-ATP channels towards ATP-induced inhibition was partially restored by addition of purified actin subunits (200 mu g ml(-1)). 6. Cytochalasin B (10 mu M), another actin filament disrupter, but neither taxol nor nocodazole (30-100 mu M), two antimicrotubule agents, enhanced K-ATP channel activity in the presence of ATP. 7. Hence, actin filament disrupters can attenuate the ATP-dependent inhibitory gating of K-ATP channels. This suggests the subsarcolemmal actin filament networks may be associated with the regulation of cardiac K-ATP channels.