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 micrograms 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 micrograms ml(-1)). 6. Cytochalasin B (10 microM), another actin filament disrupter, but neither taxol nor nocodazole (30-100 microM), 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 that subsarcolemmal actin filament networks may be associated with the regulation of cardiac K(ATP) channels.
Terzic
A
A
Division of Cardiovascular Diseases, Department of Medicine, Mayo Clinic, Mayo Foundation, Rochester, MN 55905, USA.
Kurachi
Y
Y
D008841:Actin Cytoskeleton / Q000187:drug effects / Q000502:physiology*; D000199:Actins / Q000187:drug effects / Q000502:physiology*; D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D003571:Cytochalasin B / Q000494:pharmacology; D003850:Deoxyribonuclease I / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D006168:Guinea Pigs; D006358:Hot Temperature; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000187:drug effects* / Q000378:metabolism*
D000199:Actins; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D003571:Cytochalasin B; D000255:Adenosine Triphosphate; D003850:Deoxyribonuclease I