Effect of 3,5,3'-Triiodothyronine Treatment on Potassium Efflux from Isolated Rat Diaphragm: Role of Increased Permeability in the Thermogenic Response*

Studies on the effect of T3 administration on the rate of passive potassium ion efflux from rat diaphragm have been carried out in an effort to define the mechanisms of the thermogenic effect of thyroid hormone. In particular, the effects of T3 on passive potassium ion movements have been examined in an attempt to distinguish between a primary stimulatory effect of thyroid hormone on active transport per se as opposed to one on passive cation permeability, in turn leading to the enhancement of steady-state ATP hydrolysis reflected in the thermogenic response. We show here that in rat diaphragm, a tissue in which previous studies have established a clear-cut thermogenic effect of thyroid hormone as well as an increase in ouabain-sensitive oxygen consumption and Na,K-ATPase activity, passive K+ efflux can be studied in vitro under conditions where fractional efflux rates are stable for prolonged periods of time and are amenable to simple and precise measurement. In this tissue, in which a primary stimulation of active transport would, if anything, be expected to retard K+ efflux by a hyperpolarization of the cell membrane, the administration of T3 is shown to result in a substantial increase in potassium efflux. It is further shown that the enhanced rate of passive potassium efflux induced by thyroid hormone is preserved in the presence of ouabain, which not only inhibits all active sodium and potassium transport, but additionally blocks pump-mediated K+-K+ exchange. It is concluded that thyroid hormone treatment results in an intrinsic increase in passive permeability to potassium ion. It is further suggested on the basis of these findings as well as from earlier observations in other systems that such an increase in monovalent cation permeability—apart from any primary increase in Na,K pump units—may account for a substantial portion of the thermogenic effect of thyroid hormone.