Adenosine slows the rate of K(+)-induced membrane depolarization in ventricular cardiomyocytes: possible implication in hyperkalemic cardioplegia.
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.
Alekseev
A E
AE
Departments of Medicine and Pharmacology, Mayo Clinic, Rochester, MN, USA.
Jovanović
A
A
López
J R
JR
Terzic
A
A
D000241:Adenosine / Q000494:pharmacology*; D000818:Animals; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D005905:Glyburide / Q000494:pharmacology; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D006324:Heart Arrest, Induced; D006352:Heart Ventricles; D006947:Hyperkalemia / Q000503:physiopathology; D008564:Membrane Potentials / Q000187:drug effects; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000494:pharmacology*; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology; D013997:Time Factors; D016277:Ventricular Function, Left
D015220:Calcium Channels; D015221:Potassium Channels; D000241:Adenosine; D011188:Potassium; D005905:Glyburide