Thyroid hormone receptors in control of heart rate.

Thyroid hormone has profound effects on cardiovascular functions, including heart rate. These effects can be mediated directly, e.g. by changing the expression of target genes in the heart through nuclear thyroid hormone receptors, or indirectly by altering the autonomic nervous systems output of the brain. The underlying molecular mechanisms as well as the cellular substrates, however, are far from being understood. In this review, we summarize the recent key findings on the individual contributions of the two thyroid hormone receptor isoforms on the regulation of heart rate, challenging the role of the pacemaker channel genes Hcn2 and Hcn4 as sole mediators of the hormone's effect. Furthermore, we discuss the possible actions of thyroid hormone on the autonomic nervous system affecting heart rate distribution, and highlight the possibility of permanent alterations in heart and brain by impaired thyroid hormone action during development as important factors to consider when analyzing or designing experiments.