Thyroid status and Na(+)-K+ pump current, intracellular sodium, and action potential duration in rabbit heart

Abstract

Thyroid status influences the abundance of Na(+)-K+ pumps in the heart. To evaluate whether this phenomenon may contribute to a dependence of the action potential duration (APD) on thyroid status, we induced hypothyroidism in a group of New Zealand White rabbits. Another group was treated similarly but also received triiodothyronine (T3). Right ventricular myocytes were isolated and voltage clamped at -40 mV. We identified Na(+)-K+ pump current (Ipump) as a ouabain-induced shift in holding current. Mean Ipump, measured using patch pipettes containing 10 mM Na+, was 0.24 +/- 0.02 pA/pF in 9 cells from 4 hypothyroid rabbits and 0.48 +/- 0.05 in 10 cells from 4 rabbits treated with T3 (P < 0.001). Because thyroid status influences Na+ influx, we measured intracellular Na+ activity (aiNa) in right ventricular papillary muscles. We found that aiNa was 5.20 +/- 0.42 mM in nine papillary muscles from seven hypothyroid rabbits and 7.62 +/- 0.69 mM in nine papillary muscles from six rabbits treated with T3 (P < 0.01). The effect of thyroid-induced changes in Ipump and aiNa on APD was stimulated with a computer model. The simulations predicted that thyroid-induced changes in Ipump can influence APD. The predicted changes were similar to changes in APD measured in isolated papillary muscles.