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Activation of ATP‐Sensitive Potassium Channels Underlies Contractile Failure in Single Human Cardiac Myocytes During Complete Metabolic Inhibition
Author(s) -
COHEN NERI M.,
LEDERER WJ,
NICHOLS COLIN G.
Publication year - 1992
Publication title -
journal of cardiovascular electrophysiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.193
H-Index - 138
eISSN - 1540-8167
pISSN - 1045-3873
DOI - 10.1111/j.1540-8167.1992.tb01096.x
Subject(s) - myocyte , medicine , glycolysis , potassium channel , membrane potential , patch clamp , oxidative phosphorylation , contraction (grammar) , electrophysiology , biophysics , endocrinology , chemistry , biochemistry , biology , metabolism
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 K aTP channel activity was described by a sigmoid curve with K i , ATP (ATP concentration required for half‐maximal inhibition of K ATP channel activity) = 8 μM and Hill coefficient (n H ) = 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 K ATP channels. ( J Cardiovasc Electrophysiol, Vol. 3, pp. 56–63, February 1992 )