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Effect of simulated I_to on guinea pig and canine ventricular action potential morphology

¹Department of Pharmacology and Cell Biophysics, University of Cincinnati College of Medicine, Cincinnati, Ohio; and ²Department of Biology, Emory University, Atlanta, Georgia

Submitted 20 January 2006 ; accepted in final form 14 March 2006

The transient outward current (I_to) is a major repolarizing current in the heart. Marked reduction of I_to density occurs in heart failure and is accompanied by significant action potential duration (APD) prolongation. To understand the species-dependent role of I_to in regulating the ventricular action potential morphology and duration, we introduced simulated I_to conductance in guinea pig and canine endocardial ventricular myocytes using the dynamic clamp technique and perforated patch-clamp recordings. The effects of simulated I_to in both types of cells were complex and biphasic, separated by a clear density threshold of 40 pA/pF. Below this threshold, simulated I_to resulted in a distinct phase 1 notch and had little effect on or moderately prolonged the APD. I_to above the threshold resulted in all-or-none repolarization and precipitously reduced the APD. Qualitatively, these results agreed with our previous studies in canine ventricular cells using whole cell recordings. We conclude that 1) contrary to previous gene transfer studies involving the Kv4.3 current, the response of guinea pig ventricular myocytes to a fully inactivating I_to is similar to that of canine ventricular cells and 2) in animals such as dogs that have a broad cardiac action potential, I_to does not play a major role in setting the APD.

dynamic clamp; transient outward current; ventricular myocytes

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