Activation of ATP‐Sensitive Potassium Channels Underlies Contractile Failure in Single Human Cardiac Myocytes During Complete Metabolic Inhibition

NERI M. COHEN, WJ LEDERER, COLIN G. NICHOLS

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

ATP‐Sensitive Potassium Channels in Human Heart. Introduction: The purpose of this study was to examine the electrophysiologic derangements that underlie contractile failure in single human heart muscle cells exposed to metabolic inhibition. Methods and Results: Single myocytes were isolated from right atrial appendage specimens obtained intraoperatively from patients undergoing routine cardiac surgery. On exposure to lO‐mM 2‐deoxyglucose (to inhibit glycolysis) and 2‐mM cyanide (to inhibit oxidative phosphorylation), twitch shortening decreased to undetectable levels over 5–6 minutes. The action potential duration declined in parallel with the contractile failure. Using voltage clamp depolarizations of a fixed duration the twitch was maintained in metabolic blockade until the development of maintained (rigor) contracture. At this time a large increase in K+ conductance, which can be attributed to the activation of ATP‐sensitive K + channels (K ATP channels), was measured. In isolated inside‐out membrane patches, the ATP dependence of KaTP channel activity was described by a sigmoid curve with Ki,ATP (ATP concentration required for half‐maximal inhibition of K ATPchannel activity) = 8 μM and Hill coefficient (nH) = 1.2. The single channel current‐voltage relationship reversed close to the K + equilibrium potential and the conductance was approximately linear (g = 29 pS) over the voltage range included in the action potential (‐60 m V to +20 mV). Conclusion: In human atrial cardiac myocytes subjected to complete metabolic inhibition, contractile failure is caused by action potential shortening resulting from an increase in K + conductance presumably through the activation of KATP channels. (J Cardiovasc Electrophysiol, Vol. 3, pp. 56–63, February 1992)

Original languageEnglish
Pages (from-to)56-63
Number of pages8
JournalJournal of cardiovascular electrophysiology
Volume3
Issue number1
DOIs
StatePublished - Feb 1992
Externally publishedYes

Keywords

  • action potential
  • adenosine triphosphate
  • contraction
  • human heart
  • metabolism
  • single heart cells

Fingerprint Dive into the research topics of 'Activation of ATP‐Sensitive Potassium Channels Underlies Contractile Failure in Single Human Cardiac Myocytes During Complete Metabolic Inhibition'. Together they form a unique fingerprint.

  • Cite this