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

Whole-cell recording methods and fluorescence microscopy were used to study the effects of acute exposure to thyroid hormone (T-3) on cat atrial myocytes. Acute exposure (similar to5 min) to 10 nm T-3 significantly increased tetrodotoxin (TTX)-sensitive inward Na+ current (I-Na) at voltages between -40 and +20 mV. At maximal I-Na activation (-40 mV) T-3 increased peak I-Na by 32 %. T-3 had no effect on the time course of I-Na decay, voltage dependence of activation, inactivation, or recovery from inactivation. Comparable exposures to reverse T-3 (rT(3)) or T-4 had no effect on I-Na. L-type Ca2+ current was unaffected by acute exposure to T-3. T-3-induced increases in I-Na were unaffected by 50 mum nickel, a blocker of T-type Ca2+ current. T-3 significantly increased cell shortening (+62 %) and could elicit spontaneous action potentials arising from Ca2+-mediated after-depolarizations. T-3 (but not rT(3)) significantly increased baseline intracellular Ca2+, release of Ca2+ from sarcoplasmic reticulum (SR) and caffeine (10 mm) -induced release of SR Ca We conclude that acute T, exposure increases Na+ influx via I-Na and thereby stimulates reverse-mode Na+-Ca2+ exchange to increase intracellular Ca2+ content and release. As a result, T-3 increases contraction strength, and can initiate Ca2+-mediated arrhythmic activity. Acute non-genomic effects of T-3 can contribute to the positive inotropy and sinus (atrial) tachycardia traditionally attributed to chronic, genomic effects of elevated thyroid hormone on atrial muscle.