Changes in thyroid state affect pH(i) and Na(i)+ homeostasis in rat ventricular myocytes

Abstract

We have tested the hypothesis that thyroid state may influence both the flow of cellular Ca2+ and the myofilament response to Ca2+ by effects on intracellular pH (pH(i)) and Na+ (Na(i)+). Single cardiac myocytes isolated from hypothyroid, euthyroid and hyperthyroid animals were loaded with fura-2/AM (Ca(i)2+ probe), BCECF/AM (pH(i) probe) or SBFI/AM (Na(i)+ probe). Compared with hypothyroid animals, myocytes isolated from hyperthyroid rat hearts demonstrated a significant: (1) increase in extent of shortening; (2) decrease in the time to peak contraction: (3) increase in the peak amplitude of the fura-2 fluorescence ratio; (4) decrease in pH(i) (ΔpH(i) = 0.19 ± 0.05); and (5) increase in Na(i)+ (ΔNa(i)+ = 2.88 ± 0.55 mM). We have also compared pH(i) in Langendorff perfused hypo- and hyperthyroid rat hearts using NMR. We have found that hyperthyroid hearts are 0.15 ± 0.03 pH units more acidic than hypothyroid hearts. Analysis of mRNA levels demonstrated that hyperthyroidism increased expression of both the Na+/Ca2+ exchanger and Na+/H+ antiporter, and decreased expression of Na+ channel mRNAs. These changes appear partially responsible for the observed changes in Na(i)+ and pH(i). Our results provide the first evidence that changes 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(i)2+ mediated by altered pH(i) and Na(i)+.