Deviation from normal thyroid hormone (TH) homeostasis causes profound alterations in many organ systems; in particular, cardiovascular ionotropism and chronotropism are significantly affected. It has been postulated that TH action is via the sympathetic nervous system. But after numerous studies, the mechanism of that action has not been clearly elucidated. Here we report preliminary evidence revealing and inverse relationship of TH status and cardiac calcium channels, as demonstrated by (3H)- nitrendipine binding. These data, along with recent literature, point t TH influence upon cellular calcium regulation. We suggest that TH may be exerting its adrenergic-like effects through a change in cellular calcium dynamics. In this application, we propose to further study the time course, level, tissue specificity and receptor specificity of TH action on calcium channel regulation in excitable tissues of rat. We will correlate channel number with channel function, utilizing tension and voltage dependent 45Ca flux studies. Accordingly, clinical studies are proposed investigating dihydropyridine efficacy in (1) ameliorating symptoms associated with thyroid disorders and (2) as cardiovascular agents in patients with concombinant cardiovascular and thyroid disease. These proposed studies of Ca2+ channel ligand binding, pharmacology, and calcium regulation, in TH altered states will contribute useful, relevant information to both clinician and basic scientist.
