Cardiac ion channel expression and contractile function in mice with deletion of thyroid hormone receptor α or β

B. Gloss, S. U. Trost, W. F. Bluhm, E. A. Swanson, R. Clark, R. Wlnkfein, K. M. Janzen, W. Giles, O. Chassande, J. Samarut, W. H. Dillmann

Research output: Contribution to journalArticlepeer-review

147 Scopus citations

Abstract

Cardiac myocytes express the two thyroid hormone receptors (T3Rs), T3Rα and T3Rβ. However, which isoform contributes to specific, T3-induced alterations of cardiac function remains unclear. Here, we used individual T3R isoform knockout (KO) mice to study the effects of T3Rα and T3Rβ in the heart. Our findings indicate that potassium channel genes that code for K+ channels involved in action potential repolarization, like KV 4.2 and minK, are T3Rα targets. Both are markedly regulated by thyroid status. The recently identified cyclic nucleotide-gated channels, HCN2 and HCN4, are targets of T3Rα and are unchanged in a euthyroid T3Rβ KO. However, these transcripts respond markedly to altered T3 signaling concomitant with bradycardia in T3Rα KO and hypothyroid animals, as well as tachycardia in hyperthyroid T3Rβ KO mice. SERCA2a and myosins are T3 regulated and were also targets of T3Rα, and the papillary muscles of αKO animals showed a slowed rate of force development. Because of the absence of significant cardiac effects in euthyroid T3Rβ KO mice, we determined messenger RNA levels for both T3Rα and T3Rβ in the heart, We found that T3Rβ is present at a 1:3 ratio to T3Rα1. We conclude that the cardiac phenotype regulated by T3 is predominantly mediated by T3Rα and that the lack of T3Rα cannot be compensated by T3Rβ in the heart.

Original languageEnglish (US)
Pages (from-to)544-550
Number of pages7
JournalEndocrinology
Volume142
Issue number2
DOIs
StatePublished - 2001
Externally publishedYes

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