Activation of sodium transport mediates regulation of thyroid follicle volume in response to hypotonic media

Abstract

The thyroid epithelium possesses a bidirectional fluid transport system capable of absorbing Na+ and secreting Cl-. In the present studies we have examined its possible role in the regulation of thyroid follicular size. When exposed to hypotonic media (200 mosM) cultured porcine thyroid follicles first swelled and then displayed a regulatory volume decrease (RVD) over 60 min. This was associated with a transient depolarization of the transepithelial potential difference (TEP) and subsequent hyperpolarization with a time course similar to RVD. Phenamil (1 microM), an antagonist of epithelial Na+ channels, did not affect initial swelling but prevented the subsequent follicular RVD. Phenamil abolished hyperpolarization of TEP, but the loop diuretic bumetanide, which inhibits Cl- secretion in thyroid cells, did not prevent it. Exposure to hypotonic medium produced a slow hyperpolarization of the intracellular potential (basolateral membrane potential) consistent with an increase in basolateral membrane K+ conductance. Ba2+ and quinidine, which are known to inhibit K+ channels in epithelia, prevented RVD. Addition of the K+ ionophore valinomycin (1 microM) caused follicle shrinkage that was prevented by phenamil (1 microM). We conclude that cultured follicles respond to hypotonically induced stretch by activating outwardly directed Na+ transport through a mechanism which involves change in the basolateral K+ conductance. This response would be characteristic of a system that controlled follicle volume. However, it is not clear from these studies whether the cells responded primarily to the increase in follicle volume or to the change in cell volume that is expected to accompany hypotonic challenge.