B. Orourke et al., OSCILLATIONS OF MEMBRANE CURRENT AND EXCITABILITY DRIVEN BY METABOLICOSCILLATIONS IN HEART-CELLS, Science, 265(5174), 1994, pp. 962-966
Periodic changes in membrane ionic current linked to intrinsic oscilla
tions of energy metabolism were identified in guinea pig cardiomyocyte
s. Metabolic stress initiated cyclical activation of adenosine triphos
phate-sensitive potassium current and concomitant suppression of depol
arization-evoked intracellular calcium transients. The oscillations in
membrane current and excitation-contraction coupling were linked to o
scillations in the oxidation state of pyridine nucleotides but were no
t driven by pacemaker currents or alterations in the concentration of
cytosolic calcium. Interventions that altered the rate of glucose meta
bolism modulated the oscillations, suggesting that the rhythms origina
ted at the level of glycolysis. The energy-driven oscillations in pota
ssium currents produced cyclical changes in the cardiac action potenti
al and thus may contribute to the genesis of arrhythmias during metabo
lic compromise.