Abstract
It has been proposed that the hyperthyroid (HT) state has a direct effect on myocardial contractility by enhancing the function of the sarcoplasmic reticulum (SR) ATP-dependent Ca pump. We tested this hypothesis by simultaneously measuring cytosolic Ca transients and cell length in single ventricular myocytes isolated from HT rats. Rats were made HT by daily injection of 1 mg thyroxin for 18 days and cells were isolated by enzymatic dissociation. Ca transients were measured with fura-2 and cell length by a video edge detector during field stimulation over a range of frequencies (0.3–6 Hz). Experiments were performed at room temperature. HT cells showed a marked decrease in the time to reach peak shortening and 50% and 90% relaxation compared to cells from euthyroid (ET) rats. This effect on cell length corresponded to identical changes in the Ca transients. With higher stimulation frequencies, ET cells displayed increasing diastolic Ca levels as well as larger Ca transients with systole consistent with enhanced Ca loading of the SR. The HT cells did not have an appreciable change in diastolic or systolic Ca levels with higher stimulation frequencies. Additionally, the HT celis remained viable and without evidence of Ca overload at significantly higher frequencies than ET celis. Thus, although the HT cells did not show the initial enhanced contractility of the ET cells in response to higher stimulation frequencies, they were much more resistant to Ca overload which eventually caused functional deterioration in the ET cells at the highest range of stimulation frequencies. This finding, in addition to the marked increase in the rates of diastolic relaxation and Ca sequestration in the HT celis can be explained by enhanced activity of the SR-bound Ca pump. A model for the effect of the HT state on ventricular function mediated via the SR pump is proposed.
Published Version
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