Functional linkage of the cardiac ATP-sensitive K+ channel to the actin cytoskeleton.
The role of the cytoskeleton in the rundown and reactivation of adenosine triphosphate (ATP) sensitive K+ channels (KATP channels) was examined by perturbing selectively the intracellular surface of inside-out membrane patches excised from guinea-pig ventricular myocytes. Actin filament-depolymerizing agents (cytochalasins and desoxyribonuclease I) accelerated channel rundown, while actin filament stabilizer (phalloidin) or phosphatidylinositol biphosphate (PIP2; inhibitor of F-actin-severing proteins) inhibited spontaneous and/or Ca2+-induced rundown. When rundown was induced by cytochalasin D or by long exposure to high Ca2+, channel activity could not be restored by exposure to MgATP, but application of F-actin with MgATP could reinstitute channel activity. The processes of rundown and reactivation of cardiac KATP channels may thus be influenced by the assembly and disassembly of the actin cytoskeletal network, which provides a novel regulatory mechanism of this channel.
Furukawa
T
T
Department of Autonomic Physiology, Medical Research Institute, Tokyo Medical and Dental University, Japan.
Yamane
T
T
Terai
T
T
Katayama
Y
Y
Hiraoka
M
M
D000199:Actins / Q000502:physiology*; D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D003078:Colchicine / Q000494:pharmacology; D015638:Cytochalasin D / Q000494:pharmacology; D003599:Cytoskeleton / Q000737:chemistry* / Q000502:physiology*; D006168:Guinea Pigs; D006321:Heart / Q000502:physiology*; D006352:Heart Ventricles / Q000737:chemistry / Q000166:cytology; D009206:Myocardium / Q000737:chemistry / Q000166:cytology*; D019269:Phosphatidylinositol 4,5-Diphosphate; D018129:Phosphatidylinositol Phosphates / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects*; D016276:Ventricular Function
D000199:Actins; D019269:Phosphatidylinositol 4,5-Diphosphate; D018129:Phosphatidylinositol Phosphates; D015221:Potassium Channels; D015638:Cytochalasin D; D000255:Adenosine Triphosphate; D003078:Colchicine