Hyperthyroid adult rat cardiomyocytes. II. Single cell electrophysiology and free calcium transients

Abstract

The effects of hyperthyroidism on electrophysiological properties and intracellular free calcium transients in single adult rat cardiomyocytes were studied using conventional microelectrodes and time-resolved single cell fura-2 fluorescence microscopy. Under control conditions, resting membrane potentials and triggered action potentials were not different in euthyroid and hyperthyroid myocytes. Calcium transients produced by electrical stimulation, however, were markedly abbreviated in hyperthyroid myocytes. During a train of stimuli, the duration of the calcium transients at half peak amplitude (half time) was 124 +/- 14 ms at the fifth beat in hyperthyroid cells vs. 287 +/- 35 ms in euthyroid cells. Isoproterenol (1 microM) prolonged time to 50% repolarization (APD50) of the action potentials and increased the peak calcium transients in both euthyroid and hyperthyroid myocytes. It also shortened the half time of the calcium transients in euthyroid myocytes but had little effect on the half time in hyperthyroid cells. These data are consistent with the electrophysiology and mechanical performance in intact euthyroid and hyperthyroid cardiac tissues, and the intrinsic changes in hyperthyroid tissues can therefore be illustrated in single ventricular myocytes. Furthermore, the results suggest that alterations in intracellular calcium handling by sarcoplasmic reticulum may account for contractile changes of the heart induced by hyperthyroidism.

Thyroid hormone regulation of cardiac bioenergetics: role of intracellular creatine

“…This results from a dual action of the hormone: a direct one, which is due to stimulation of cardiomyocyte metabolism, and a second, indirect one, which occurs in response to increased demand of peripheral tissues for oxygen and substrates and for the removal of waste products (5,10). The combination of these effects, at least during the early phase of hyperthyroidism, leads to increased "contractility" of the hyperthyroid heart, which is manifested by positive changes in virtually all measurable parameters of cardiac muscle function (1,3,5,6,10,21,29,30,46). Excess thyroid hormone is associated with an increase in the number and volume of mitochondria in cardiac myocytes and skeletal muscle, and the resultant stimulation of oxidative phosphorylation is associated with increased numbers of respiratory units per milligram mitochondrial protein with little or no change in the phosphorylation-to-oxidation ratio (5,10,30,46).…”