Cellular electrophysiological aspects of myocardial protection.
Oxygen radicals (OR) generated at the time of reflow of the ischaemic myocardium may cause 'reperfusion injury'. To protect myocardium from this injury, it is important to understand how OR cause their deleterious effects on myocytes. Here we describe the basic electrophysiological alterations caused by OR in patch-clamped ventricular myocytes isolated from the rat heart. Oxygen radicals generated by dihydroxyfumarate (DHF) caused a lengthening of action potential duration (APD) and the appearance of arrhythmogenic alterations such as early and delayed afterdepolarizations. Prolongation of APD was accompanied by a reduction in calcium and potassium currents. When intracellular calcium levels were kept constantly low by 500 microM EGTA in the pipette solution, the effects of DHF on action potential duration and the occurrence of early afterdepolarizations were largely prevented. It is concluded that exposure to OR may induce electrophysiological alterations in isolated myocytes. They are related to changes in specific ionic currents and in levels of intracellular calcium.
Mugelli
A
A
Department of Pharmacology, University of Firenze, Italy.
Cerbai
E
E
Barbieri
M
M
Li
Q
Q
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002118:Calcium / Q000378:metabolism; D005609:Free Radicals; D005650:Fumarates / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D010100:Oxygen / Q000378:metabolism; D051381:Rats
D005609:Free Radicals; D005650:Fumarates; C005998:dihydroxyfumarate; D010100:Oxygen; D002118:Calcium