Functional communication between cardiac ATP-sensitive K+ channel and Na/K ATPase

Kunihiko Tsuchiya, Minoru Horie, Tetsuya Haruna, Tomohiko Ai, Toshihisa Nishimoto, Hisayoshi Fujiwara, Shigetake Sasayama

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

Introduction: Functional interaction between K(ATP) channel and Na/K ATPase was studied in single guinea pig ventricular myocytes because both membrane molecules are known to be involved in ischemic episodes. Methods and Results: K(ATP) channel currents were recorded at 36°C by using whole cell, cell-attached, inside-out, and open cell-attached modes of patch clamp techniques on enzymatically isolated ventricular myocytes. In the whole cell mode, ouabain (1μM) reversibly inhibited the K(ATP) currents induced by metabolic stress (ATP-free pipette solution and 1 mM NaCN), but not those activated by cromakalim (100 μM), a K(ATP) channel opener. In the cell- attached mode, ouabain concentration dependently inhibited K(ATP) channel opening induced by metabolic suppression (5.5 mM 2-deoxyglucose and 1 mM CN- ). Half-inhibition concentration for ouabain was 21.0 ± 5.5 nM and the Hill coefficient was 0.8 ± 0.1 (n = 26). However, ouabain did not have an effect on the channel activity induced by cromakalim (100 μM). In the inside-out mode, ouabain applied to the internal side of membrane did not affect the channel. In the open cell-attached mode made by preincubation with streptolysin-O (0.08 U/mL), the K(ATP) channels were not activated by the metabolic inhibitors but were by reducing extracellular ATP concentrations, because subsarcolemmal ATP concentration could be controlled through tiny membrane holes. The channels thus activated were not suppressed by ouabain. Conclusion: The inhibition of Na/K ATPase by ouabain appeared to block the K(ATP) channels by accumulating subsarcolemmal ATP caused by a decrease of the transition from ATP to ADP. In the presence of ischemic episodes, the administration of digitalis compounds may affect the opening of K(ATP) channels, which is primarily protective against the development of irreversible myocardial damage.

Original languageEnglish (US)
Pages (from-to)415-422
Number of pages8
JournalJournal of Cardiovascular Electrophysiology
Volume9
Issue number4
DOIs
StatePublished - Jan 1 1998

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Keywords

  • ATP-sensitive potassium channel
  • Na/K ATPase
  • Subsarcolemmal ATP

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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