The effect of inhibition of mitochondrial energy metabolism on the transient inward current of isolated guinea-pig ventricular myocytes.

Delayed afterdepolarizations (DADs) might underlie ischemic or reperfusion arrhythmias (Ferrier et al., 1985; Coetzee and Opie, 1987). These DADs are the result of a transient inward current iti, which is caused by instability of the intracellular level of free Ca2+ (Cai) due to an oscillatory release of Ca from the sarcoplasmic reticulum (Kass et al., 1978). DADs are known to be abolished by hypoxia and by metabolic inhibition (Di Gennaro et al., 1987; Coetzee and Opie, 1987), which could be caused by a number of different mechanisms: (1) The large increase of potassium conductance associated with metabolic inhibition (Vleugels et al., 1980; Isenberg et al., 1983) could prevent iti from causing a marked depolarization, and would thus "mask" the DADS. (2) Although metabolic inhibition will eventually result in an increase of Cai, a temporary decrease could initially take place, thereby minimizing the Ca instability. Two mechanisms are known which might produce such an effect: Firstly, the shortening of the action potential which occurs during metabolic inhibition will markedly reduce the time during which Ca channels remain open, thereby causing a diminished total Ca influx during the action potential (Isenberg et al., 1983; Noma and Shibasaki, 1985; Kakei et al., 1985). Secondly, a direct reduction of iCa by a decrease in ATP concentration, described by Irisawa and Kokubun (1983), could also contribute to a decreased Ca load. (3) Metabolic inhibitors could possibly interfere with the cycling of Ca between different compartments within the cell, thereby altering the temporal variation in Cai, and thus influencing iti.(ABSTRACT TRUNCATED AT 250 WORDS)