MECHANISMS OF THYROID-HORMONE CONTROL OVER SENSITIVITY AND MAXIMAL CONTRACTILE RESPONSIVENESS TO BETA-ADRENERGIC AGONISTS IN ATRIA

This paper discusses the mechanisms of two basic effects of thyroid ho rmones on atrial responses to beta-adrenergic agonists, i.e. increased inotropic sensitivity and decreased maximal contractile responsivenes s. The increased sensitivity of atria to beta-adrenergic agonists unde r thyroid hormones appears to be related to increases in beta-adrenoce ptor density and G(s)/G(i) protein ratio, leading to activation of G(s )-mediated pathway, but suppression of G(i)-mediated pathway of adenyl ate cyclase regulation. Therefore, the i/c concentrations of cAMP and corresponding inotropic responses achieve their maximums at lower dose s of beta-adrenergic agonist. Thyroid hormones also decrease the expre ssion of phospholamban, but increase the expression of sarcoplasmic re ticulum Ca2+-pump. As a result, the basal activity of sarcoplasmic ret iculum Ca2+-pump increases, but its beta-adrenergic activation through phosphorylation of phospholamban decreases. It is suggested that thes e changes are causal for decreased maximal inotropic and lusitropic re sponses of atria to beta-adrenergic agonists.