The effects of inhibition of oxidative phosphorylation by 1 mM
cyanide (CN) and of glycolysis by 20 mM
2-deoxyglucose (2DG) on contraction and relaxation of cultured monolayers of chick embryo heart cells were determined. Exposure to these agents first induced a gradual decline in contractility and a transient impairment of relaxation. Spontaneous beating then ceased, associated with increased relaxation, followed by a marked and prolonged
contracture. This
contracture was completely reversible after washout of metabolic inhibitors. The effects of
calcium flux inhibitors on the time course of development of
contracture were studied.
Verapamil, which inhibits Ca influx via the slow Ca channel, delayed the onset of
contracture when used in pretreatment, but had no effect if added to cultures after exposure to CN + 2DG.
Lanthanum, which inhibits Ca influx both via the slow Ca channel and via Na-Ca exchange, delayed onset of
contracture if added after exposure to CN and 2DG, but accelerated
contracture if added prior to treatment with CN + 2DG. Cellular exchangeable
calcium content, measured after exposure to CN and 2DG for the same time period that produced
contracture, was reduced compared to the control level while unidirectional Ca influx rate was not measurably altered. Exchangeable Ca content was unaffected by pretreatment with
verapamil and La, but was reduced if cells were exposed to La after metabolic inhibition. These findings suggest that after metabolic inhibition intracellular storage capacity for Ca+ is reduced in cultured heart cells. Ca influx via the slow Ca channel after metabolic inhibition does not appear to contribute to development of
contracture in this model system. However, Ca entry via Na-Ca exchange may accelerate cellular
contracture developing after metabolic inhibition of
ATP production.