Heterogeneity and function of KATP channels in canine hearts

Hai Xia Zhang, Jonathan R. Silva, Yu Wen Lin, John W. Verbsky, Urvi S. Lee, Evelyn M. Kanter, Kathryn A. Yamada, Richard B. Schuessler, Colin G. Nichols

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

Background The concept that pore-forming Kir6.2 and regulatory SUR2A subunits form cardiac ATP-sensitive potassium (KATP) channels is challenged by recent reports that SUR1 is predominant in mouse atrial K ATP channels. Objective To assess SUR subunit composition of K ATP channels and consequence of KATP activation for action potential duration (APD) in dog hearts. Methods Patch-clamp techniques were used on isolated dog cardiomyocytes to investigate KATP 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 KATP activation on APD. Results 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 KATP 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 KATP current, a result reproduced in silico by using a canine action potential model (Hund-Rudy) to simulate epicardial and endocardial myocytes. Conclusions Even a small fraction of KATP activation significantly shortens APD in a manner that depends on existing heterogeneity in KATP current and APD.

Original languageEnglish
Pages (from-to)1576-1583
Number of pages8
JournalHeart rhythm
Volume10
Issue number10
DOIs
StatePublished - Oct 2013

Keywords

  • ATP-sensitivepotassiumchannel
  • Actionpotentialduration
  • Canine
  • Diazoxide
  • Metabolicinhibition
  • Modelsimulation
  • Myocyte
  • Patch-clamptechnique
  • Pinacidil
  • Sulfonylureareceptor

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