Effects of metabolic blockade on intracellular calcium concentration in isolated ferret ventricular muscle

Abstract

Tension and intracellular free calcium concentration [( Ca2+]i) were measured in isolated ferret papillary muscles. When both anaerobic glycolysis and oxidative phosphorylation were prevented (metabolic blockade), there was a rapid decline of both developed tension and systolic [Ca2+]i signals. Subsequently, resting tension increased, and after a further delay, resting [Ca2+]i also rose. When oxidative metabolism was restarted after a period of metabolic blockade that was sufficient to elevate both resting tension and [Ca2+]i, a variable recovery of mechanical function occurred. In preparations that showed recovery, resting tension declined toward control level, and there was considerable recovery of developed tension. [Ca2+]i initially fell, but it then rose to a level similar to that at the end of the preceding period of metabolic blockade and exhibited large variations in amplitude with frequency components in the range 0.2-1 Hz. This elevated [Ca2+]i gradually declined. Arrhythmias were often present during this recovery period and appeared to be triggered by the spontaneous increases in [Ca2+]i. In preparations that failed to recover, resting tension remained elevated or increased, and developed tension showed little recovery. Such preparations showed larger rises in [Ca2+]i both during and after metabolic blockade, and [Ca2+]i continued to rise when oxidative metabolism was restarted. In experiments in which Na-Ca exchange was inhibited (by replacement of sodium by lithium or by the application of nickel), the rise of [Ca2+]i when oxidative metabolism was restarted was reduced, but recovery of mechanical function was improved. The correlation between elevated [Ca2+]i on reactivation of oxidative metabolism and failure of recovery of mechanical function suggests that elevated [Ca2+]i has a direct role in preventing the recovery of mechanical function.