Thyroid hormone effects on intracellular calcium and inotropic responses of rat ventricular myocardium.
To examine the mechanisms by which thyroid hormone modulates the inotropic state of rat myocardium, we studied the effects of thyroid state on isolated rat left ventricular papillary muscle function and intracellular calcium transients in the baseline state and in response to calcium and isoproterenol. Marked differences in contractile state of papillary muscles from hypothyroid and thyroid hormone-treated rats seen under baseline conditions (1.0 mM bath calcium, 30 degrees C, stimulation rate 12/min) do not appear to be due to differences in intracellular calcium concentration ([Ca2+]i) or to changes in myofilament calcium sensitivity but correlate with shifts in myosin isozyme distribution. In response to superimposed inotropic interventions (calcium, 0.625-5.0 mM, or isoproterenol, 10(-8)-10(-6) M), myocardial thyroid state modulates peak [Ca2+]i and inotropy, both of which are increased in thyroid hormone-treated relative to hypothyroid myocardium. The change in inotropy appears to be proportional to peak [Ca2+]i, whether mediated directly by calcium or as a result of beta-adrenergic stimulation. Thus, whereas baseline differences between hypothyroid and thyroid hormone-treated myocardium appear to be due to differences in myosin isozymes and presumed changes in adenosinetriphosphatase activity and cross-bridge cycling, superimposed inotropic responses appear to be mediated by changes in [Ca2+]i.
Bing
O H
OH
Department of Veterans Affairs Medical Center, Boston, Massachusetts, 02130.
Hague
N L
NL
Perreault
C L
CL
Conrad
C H
CH
Brooks
W W
WW
Sen
S
S
Morgan
J P
JP
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D006321:Heart / Q000033:anatomy & histology / Q000187:drug effects; D006652:Histological Techniques; D007425:Intracellular Membranes / Q000378:metabolism*; D007537:Isometric Contraction; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000378:metabolism*; D009218:Myosins / Q000378:metabolism; D009929:Organ Size; D051381:Rats; D011921:Rats, Inbred WKY; D013963:Thyroid Hormones / Q000494:pharmacology*; D016276:Ventricular Function
D013963:Thyroid Hormones; D009218:Myosins; D007545:Isoproterenol; D002118:Calcium