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

摘要

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 nm 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 μm 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 mm)-induced release of SR Ca²⁺. We conclude that acute T₃ 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, 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.