Activation of pyruvate dehydrogenase by electrical stimulation, and low-Na + perfusion of guinea-pig heart

Abstract

(1) Electrical stimulation (2 Hz) of guinea-pig hearts, perfused with medium containing 11 mM D-glucose plus 0.1 mM octanoate as substrate, resulted in an increase in the percentage of pyruvate dehydrogenase in the active form (PDH a) from 16 to 68%. (2) Rapid isolation of mitochondria by a technique designed to minimize net loss or gain of Ca 2+ revealed an increase in mitochondrial Ca 2+ content of the stimulated hearts, as measured with 45Ca (2.74 ± 0.27 versus 1.37 ± 0.11 nmol/mg protein; stimulated versus rested). (3) Perfusion of rested hearts with a medium containing a reduced Na + concentration (20 mM, with the remainder replaced with Li +) also gave increased values of PDH a content (30.9% versus 16% for the normal, physiological medium). This procedure is known to raise cytosol Ca 2+ concentrations and would be expected to give mitochondrial Ca 2+ loading. (4) These results are consistent with a role of mitochondrial Ca 2+ in activating pyruvate dehydrogenase in the intact heart.