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Heart Rhythm. 2013 Oct;10(10):1576-83. doi: 10.1016/j.hrthm.2013.07.020. Epub 2013 Jul 17.

Heterogeneity and function of K(ATP) channels in canine hearts.

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Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, Missouri; Center for the Investigation of Membrane Excitability Diseases, Washington University School of Medicine, St. Louis, Missouri.



The concept that pore-forming Kir6.2 and regulatory SUR2A subunits form cardiac ATP-sensitive potassium (K(ATP)) channels is challenged by recent reports that SUR1 is predominant in mouse atrial K(ATP) channels.


To assess SUR subunit composition of K(ATP) channels and consequence of K(ATP) activation for action potential duration (APD) in dog hearts.


Patch-clamp techniques were used on isolated dog cardiomyocytes to investigate K(ATP) channel properties. Dynamic current clamp, by injection of a linear K(+) conductance to simulate activation of the native current, was used to study the consequences of K(ATP) activation on APD.


Metabolic inhibitor (MI)-activated current was not significantly different from pinacidil (SUR2A-specific)-activated current, and both currents were larger than diazoxide (SUR1-specific)-activated current in both the atrium and the ventricle. Mean K(ATP) conductance (activated by MI) did not differ significantly between chambers, although, within the ventricle, both MI-induced and pinacidil-induced currents tended to decrease from the epicardium to the endocardium. Dynamic current-clamp results indicate that myocytes with longer baseline APDs are more susceptible to injected K(ATP) current, a result reproduced in silico by using a canine action potential model (Hund-Rudy) to simulate epicardial and endocardial myocytes.


Even a small fraction of K(ATP) activation significantly shortens APD in a manner that depends on existing heterogeneity in K(ATP) current and APD.


4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid; ANOVA; AP; APD; ATP-sensitive potassium; ATP-sensitive potassium channel; Action potential duration; CL; Canine; Diazoxide; EGTA; Endo; Epi; HEPES; I(Kr); I(Ks); I(to); K(ATP); K(ATP-INJ); MI; Metabolic inhibition; Mid; Model simulation; Myocyte; Patch-clamp technique; Pinacidil; Sulfonylurea receptor; action potential; action potential duration; analysis of variance; cycle length; endocardial/endocardium; epicardial/epicardium; ethylene glycol-bis(2-aminoethylether)-N,N,N′,N′-tetraacetic acid; metabolic inhibitor; mid-myocardial/mid-myocardium; rapid delayed rectifier current; simulated ATP-sensitive potassium current; slow delayed rectifier current; transient outward current

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