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 functional interaction between the sulfonylurea receptor (SUR) and the ATP-sensitive K+ (KATP) channels. Isolated rate ventricular cardiomyocytes were studied using open cell-attached patches for single-channel recording. Bath application of DNase I (100 microg/ml) or cytochalasin D (10 microM) stimulated the KATP channel activities (in presence of 30 microM ATP), and these channels became resistant to inhibition by tolbutamide (0.5 mM). After exposure to tolbutamide, the relative NPo 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 DNase I or cytochalasine D (*P < 0.05 vs. control). The inhibitory action of glibenclamide (10 microM) on the KATP channels was also attenuated by DNase I. Thus, the disruption of the actin cytoskeleton attenuates the ability of SUR to inhibit the opening of KATP channels.
Yokoshiki
H
H
Department of Molecular and Cellular Physiology, College of Medicine, University of Cincinnati, PO Box 670576, Cincinnati, Ohio 45267-0576, USA.
Katsube
Y
Y
Sunugawa
M
M
Seki
T
T
Sperelakis
N
N
D000199:Actins / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D015638:Cytochalasin D / Q000494:pharmacology*; D003599:Cytoskeleton / Q000187:drug effects; D003851:Deoxyribonucleases / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects*; D015221:Potassium Channels / Q000187:drug effects*; D051381:Rats; D013453:Sulfonylurea Compounds / Q000494:pharmacology*
D000199:Actins; D015221:Potassium Channels; D013453:Sulfonylurea Compounds; D015638:Cytochalasin D; D000255:Adenosine Triphosphate; D003851:Deoxyribonucleases