Thyroid hormone modulates membrane currents in guinea-pig ventricular myocytes

Summary

Thyroid hormones have been previously shown to alter cardiac electrophysiological and mechanical properties in humans and in experimental animals. To investigate electrophysiological mechanisms responsible for some of these alterations, we recorded action potentials and membrane currents from isolated ventricular myocytes obtained from euthyroid, hypothyroid and hyperthyroid guinea-pigs. Hyperthyroidism was induced by injecting 150 μg/kg triiodothyronine for 8–11 days, and hypothyroidism was induced by propylthiouracil treatment for 35–45 days. We found that the slow inward current, was increased by hyperthyroidism and decreased by hypothyroidism: in euthyroid, hyperthyroid and hypothyroid myocytes peak slow inward current was (mean ± SEM) : −1.08 ± 0.06 nA, −1.83 ±0.18^a nA and −0.64 ± 0.07^a nA, respectively (a,p < 0.005). In addition, the membrane potential at which peak slow inward current occurred was modified by the thyroid state and in euthyroid, hyperthyroid and hypothyroid myocytes it was (mean ± SEM): 4.8 ± 0.7 mV, −1.8 ± 1.6^a mV and 11.0 ± 1.4^a mV, respectively.

The outward rectifying current, was also affected by the thyroid state, and in euthyroid, hyperthyroid and hypothyroid myocytes, the amplitude atV _M = + 60 mV was (mean ± SEM): 0.51 ± 0.09 nA, 1.15 ± 0.08^a nA and 0.49 ± 0.05 nA,respectively. a,p < 0.001 compared to euthyroid myocytes. Intraperitoneal administration of a single dose of triiodothyronine to guinea-pigs, 2 h prior to the electrophysiological experiment, increased the slow inward current amplitude, as was seen with chronic hyperthyroidism, but had no significant effect on the outward current and on the action potential. Finally, action potential and membrane currents were not altered by superfusing euthyroid myocytes with 10⁻⁶ mol/l triiodothyronine for 30 min, or by introducing 10⁻⁷ mol/l triiodothyronine into the cell through the recording pipette.

From these findings we conclude that cardiac mechanical performance may be modulated by thyroid hormones through their effect on the slow inward current, while shortening of action potential duration is brought about, at least in part, by increasing the amplitude of the outward rectifying current.