Acute exposure to thyroid hormone increases Na current and intracellular Ca² in cat atrial myocytes.

Wang, Yong G.; Dedkova, Elena N.; Fiening, Jon P.; Ojamaa, Kaie; Blatter, Lothar A.; Lipsius, Stephen L.

Whole-cell recording methods and fluorescence microscopy were used to study the effects of acute exposure to thyroid hormone (T3) on cat atrial myocytes. Acute exposure (≈5 min) to 10 n m T3 significantly increased tetrodotoxin (TTX)-sensitive inward Na+ current ( INa) at voltages between −40 and +20 mV. At maximal INa activation (−40 mV) T3 increased peak INa by 32 %. T3 had no effect on the time course of INa decay, voltage dependence of activation, inactivation, or recovery from inactivation. Comparable exposures to reverse T3 (rT3) or T4 had no effect on INa. L-type Ca2+ current was unaffected by acute exposure to T3. T3-induced increases in INa were unaffected by 50 μ m nickel, a blocker of T-type Ca2+ current. T3 significantly increased cell shortening (+62 %) and could elicit spontaneous action potentials arising from Ca2+-mediated after-depolarizations. T3 (but not rT3) significantly increased baseline intracellular Ca2+, release of Ca2+ from sarcoplasmic reticulum (SR) and caffeine (10 m m)-induced release of SR Ca2+. We conclude that acute T3 exposure increases Na+ influx via INa and thereby stimulates reverse-mode Na+-Ca2+ exchange to increase intracellular Ca2+ content and release. As a result, T3 increases contraction strength, and can initiate Ca2+-mediated arrhythmic activity. Acute non-genomic effects of T3 can contribute to the positive inotropy and sinus (atrial) tachycardia traditionally attributed to chronic, genomic effects of elevated thyroid hormone on atrial muscle.

Journal of Physiology, 2003, Vol 546, Issue 2, p491

0022-3751

Academic Journal

10.1113/jphysiol.2002.032847