Adenosine slows the rate of K+-induced membrane depolarization in ventricular cardiomyocytes: Possible implication in hyperkalemic cardioplegia

Alexey E. Alekseev, Aleksandar Jovanović, Jóse R. López, Andre Terzic

Research output: Contribution to journalArticle

26 Scopus citations

Abstract

Hyperkalemic cardioplegic solutions produce cardiac arrest during open heart surgery by depolarizing the sarcolemma. A recognized adverse effect of hyperkalemic cardioplegia is the possible development of ventricular dysfunction believed to be related to intracellular Ca2+ loading, a consequence of K+-induced membrane depolarization. Adenosine has been proposed as an adjunct to hyperkalemic cardioplegic solutions. However, it is not known whether adenosine can affect K+-induced membrane depolarization, and associated intracellular Ca2+ loading. Perforated patch-clamp method, applied to isolated single guinea-pig ventricular myocytes, revealed that adenosine (1 mM) did not significantly reduce the magnitude of K+-induced membrane depolarization (35.7 ± 1.7 v 31.0 ± 1.1 mV in the absence v presence of adenosine). Yet, adenosine significantly slowed the rate of K+-induced membrane depolarization (167 ± 32.8 v 67.9 ± 12.9 mV/min in the absence v presence of adenosine) without directly affecting Ca2+, Na+, and K+ currents. Imposed ramp-pulses, with different rates (ranging from 0.33 to 0.05 V/s), but same magnitude of depolarization (100 mV), demonstrated that reduction in the rate of membrane depolarization decreases net inward Ca2+ current. Indeed, in Fluo-3 loaded ventricular myocytes, imaged by laser confocal microscopy, adenosine (1 mM) prevented K+-induced intracellular Ca2+ loading. The present findings indicate that adenosine slows the rate of K+-induced membrane depolarization, and reduces K+-induced intracellular Ca2+ loading in ventricular myocytes. Such findings support the notion that adenosine may play a cardioprotective role in hyperkalemic cardioplegia.

Original languageEnglish (US)
Pages (from-to)1193-1202
Number of pages10
JournalJournal of Molecular and Cellular Cardiology
Volume28
Issue number6
DOIs
StatePublished - Jun 1996

Keywords

  • Adenosine
  • Ca
  • Cardiomyocyte
  • Cardioplegia
  • Depolarization
  • K

ASJC Scopus subject areas

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine

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