Valinomycin blockade of myocardial slow channels is reversed by high glucose
Vogel, S.; Sperelakis, N.
American Journal of Physiology 235(1): H46-H51
1978
ISSN/ISBN: 0002-9513 PMID: 677328 Document Number: 124314
The K+ ionophore, valinomycin, blocks the Ca2+-dependent slowly-rising electrical response (slow response) induced by isoproterenol in hearts whose fast Na+ channels are voltage-inactivated by partial depolarization (to -40 mV) with elevated K+ (26 mM) solution, concomitant with a lowering of the ATP level; it also markedly shortens the ventricular action potential plateau. Other metabolic inhibitors, such as cyanide or dinitrophenol, also cause action potential shortening and slow response blockade concomitant with a lowering of the ATP level. To determine whether the electrophysiological effects of valinomycin are primarily due to an action on the surface membrane by acting as a K+ ionophore to raise K+ conductance, or on the mitochondria by uncoupling oxidative phosphorylation, a reversal of the effects of valinomycin (1-4 .mu.g/ml) in isolated perfused guinea pig and chick embryo (18-21-day-old hearts by elevation of the glucose concentration was tried. In the presence of valinomycin, glucose elevation to 27 or 55 mM (from the control level of 11 mM) reversed the shortening of the action potential plateau and restored the Ca2+-dependent slow responses within 15-30 min. Pretreatment with high glucose prevented the effects of valinomycin. Sucrose and 2-deoxy-D-glucose (55 mM) were ineffective. 2-Deoxy-D-glucose (27 mM), which inhibits glucose transport, actually blocked the slow response restored by 27 mM glucose. Insulin (100 mU/ml), which enhances glucose uptake, was capable of restoring the slow responses without elevation of glucose above the control level. Since elevated glucose uptake should lead to an increased availability of ATP, the electrophysiological effects of valinomycin are likely to be due largely to metabolic poisoning rather than to a direct effect on the sarcolemma.