1. To determine whether actin filament networks are associated with the regulation of ATP-sensitive K+ (KATP) 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 μg ml-1), which forms complexes with G-actin and prevents actin filament formation, antagonized the ATP-induced inhibition of KATP channels. 3. In the absence of ATP, DNase I did not increase KATP channel activity. 4. When denatured by boiling or co-incubated with purified actin subunits (200 μg ml-1), DNase I (100 μg ml-1) did not antagonize the ATP-induced inhibition of KATP channels. 5. The DNase I-induced decrease in the sensitivity of KATP channels towards ATP-induced inhibition was partially restored by addition of purified actin subunits (200 μg ml-1). 6. Cytochalasin B (10 μM), another actin filament disrupter, but neither taxol nor nocodazole (30-100 μM), two antimicrotubule agents, enhanced KATP channel activity in the presence of ATP. 7. Hence, actin filament disrupters can attenuate the ATP-dependent inhibitory gating of KATP channels. This suggests that subsarcolemmal actin filament networks may be associated with the regulation of cardiac KATP channels.
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