Metabolic oscillations in heart cells.
Oscillatory rhythms underlie biological processes as diverse and fundamental as neuronal firing, secretion, and muscle contraction. We have detected periodic changes in membrane ionic current driven by intrinsic oscillations of energy metabolism in guinea pig heart cells. Withdrawal of exogenous substrates initiated oscillatory activation of ATP-sensitive potassium current and cyclical suppression of depolarization-evoked intracellular calcium transients. The oscillations in membrane current were not driven by pacemaker currents or by alterations in intracellular calcium and thus represent a novel cytoplasmic cardiac oscillator. The linkage to energy metabolism was demonstrated by monitoring oscillations in the oxidation state of pyridine nucleotides. Interventions which altered the rate of glucose metabolism modulated the oscillations, suggesting that the rhythms originated at the level of glycolysis. The metabolic oscillations produced cyclical changes in electrical excitability, underscoring the potential importance of this intrinsic oscillator in the genesis of cardiac arrhythmias.
Johns Hopkins University, Department of Medicine, Baltimore, MD 21205, USA.
B
B
O'Rourke
B M
BM
Ramza
D N
DN
Romashko
E
E
Marban
D000818:Animals; D001683:Biological Clocks; D002462:Cell Membrane / Q000502:physiology; D004734:Energy Metabolism; D006168:Guinea Pigs; D006321:Heart / Q000502:physiology*; D017136:Ion Transport