HYPOTHYROIDISM DECREASES THE ATP SENSITIVITY OF K-ATP CHANNELS FROM RAT-HEART

The effects of thyroid status on the properties of ATP-sensitive potas sium channels were investigated. Single-channel recordings were made u sing excised inside-out membrane patches from enzymatically dissociate d ventricular myocytes from hearts of control and thyroidectomized rat s and each group was studied with and without administration of thyroi d hormone. In patches excised from hypothyroid myocytes the IC50 for A TP inhibition of K-ATP channels was 110 mu M. This value was 3-fold hi gher than the IC50 in control myocytes (43 mu M). Treatment of hypothy roid rats to restore physiological levels of thyroid hormone (triiodot hyronine, T-3), resulted in a return to normal ATP-sensitivity (IC50 = 46 mu M). In patches from animals rendered hyperthyroid, the IC50 for ATP was 50 mu M and this value was not significantly different from t he control. There was no difference in the cooperativity of ATP-bindin g (Hill coefficient, n(H)) among control (n(H) = 2.2), hypothyroid(n(H ) = 2.1), T-3-treated (n(H) = 2.0) and hyperthyroid groups (n(H) = 2.4 ). The unitary conductance was unchanged and there was no apparent cha nge in intraburst kinetics between examples of single K-ATP channels f rom control and hypothyroid rats. Action potentials recorded in myocyt es from hypothyroid rats were significantly shortened by 50 mu M levcr omakalim, a K-ATP channel opener (P < 0.001) but unchanged in control myocytes. We conclude that hypothyroidism significantly decreased the ATP-sensitivity of K-ATP channels, whereas the induction of hyperthyro id conditions did not alter the ATP-sensitivity of these channels. Thu s, hypothyroidism is likely to have important physiological consequenc es under circumstances in which K-ATP channels are activated, such as during ischemia.