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

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 (I(pump)) as a ouabain-induced shift in holding current. Mean I(pump), 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 (a(Na)/(i)) in right ventricular papillary muscles. We found that a(Na)/(i) 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 I(pump) and a(Na)/(i) on APD was simulated with a computer model. The simulations predicted that thyroid- induced changes in I(pump) can influence APD. The predicted changes were similar to changes in APD measured in isolated papillary muscles.