CHANGES IN THYROID STATE AFFECT PH(I) AND NA-I(+) HOMEOSTASIS IN RAT VENTRICULAR MYOCYTES

We have tested the hypothesis that thyroid state may influence both th e now of cellular Ca2+ and the myofilament response to Ca2+ by effects on intracellular pH (pH(i)) and Na+ (Na-i(+)). Single cardiac myocyte s isolated from hypothyroid, euthyroid and hyperthyroid animals were l oaded with fura-2/AM (Ca-i(2+) probe), BCECF/AM (pH(i) probe) or SBFI/ AM (Na-i(+) probe). Compared with hypothyroid animals, myocytes isolat ed from hyperthyroid rat hearts demonstrated a significant: (1) increa se in extent of shortening; (2) decrease in the time to peak contracti on; (3) increase in the peak amplitude of the fura-2 fluorescence rati o; (4) decrease in pH(i) (Delta pH(1)=0.19 +/- 0.05); and (5) increase in Na-i+ (Delta Na-i(+)=2.88 +/- 0.55 mM). We have also compared pH(i ) in Langendorff perfused hypo- 0and hyperthyroid rat hearts using NMR . We have found that hyperthyroid hearts are 0.15 +/- 0.03 pH units mo re acidic than hypothyroid hearts. Analysis of mRNA levels demonstrate d that hyperthyroidism increased expression of both the Na+/Ca2+ excha nger and Na+/H+ antiporter, and decreased expression of Na+ channel mR NAs. These changes appear partially responsible for the observed chang es in Na-i(+) and pH(i). Our results provide the first evidence that c hanges in cardiac contractility associated with altered thyroid state not only involve effects on Ca2+, but may also involve changes in the response of the myofilaments to Ca-1(2+) mediated by altered pH(i) and Na-i+. (C) 1997 Academic Press Limited.