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

Abstract

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 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.

Genistein prevents thyroid hormone‐dependent tail regression of Rana catesbeiana tadpoles by targetting protein kinase C and thyroid hormone receptor α

“…Although there is increasing evidence of an important role for phosphorylation in TH signaling (Lin et al, 1997(Lin et al, , 1998(Lin et al, , 1999bSchmidt et al, 2002;Wang et al, 2003) in in vitro and in cultured mammalian cell lines, few studies have addressed its relevance during development in vivo. In this study, by using a tadpole tail organ culture system as an experimental model, we demonstrate the possible involvement of T 3 -induced PKC tyrosine phosphorylation, which regulates TR␣ phosphorylation, thereby affecting tail regression.…”

Studies of insulin resistance in patients with clinical and subclinical hyperthyroidism

“…The lack of correlation between the abundance of GLUT3 and GLUT4 and the insulin-stimulated glucose uptake in the monocytes of the HR patients could be attributed to elevated intracellular concentration of calcium. It has been recently shown that the elevated levels of T 3 in HR increase calcium concentration in the cytosol (28). Elevated levels of cytosolic calcium can modulate insulin's ability to desphosporylate GLUT4, thus reducing its intrinsic activity and resulting in calciuminduced insulin resistance (29).…”

The Fasting Serum Insulin and Glucose Levels and the Estimated Insulin Resistance in Clinical and Subclinical Hyperthyroid Patients from Saudi Arabia

“…It is believed that the elevated cellular T 3 content can increase the cytosolic calcium concentration [26] that may cause a calcium-induced insulin resistin [27]. Furthermore, these patients are known to have significant elevation in the levels of resistin, an insulin antagonizing adipocytokine that may enhance the development of insulin resistance [28].…”