ACTIVATION OF SODIUM-TRANSPORT MEDIATES REGULATION OF THYROID-FOLLICLE VOLUME IN RESPONSE TO HYPOTONIC MEDIA

The thyroid epithelium possesses a bidirectional fluid transport syste m capable of absorbing Na+ and secreting Cl-. In the present studies w e have examined its possible role in the regulation of thyroid follicu lar 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 depo larization of the transepithelial potential difference (TEP) and subse quent hyperpolarization with a time course similar to RVD. Phenamil (1 muM), an antagonist of epithelial Na+ channels, did not affect initia l swelling but prevented the subsequent follicular RVD. Phenamil aboli shed 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 intracel lular potential (basolateral membrane potential) consistent with an in crease in basolateral membrane K+ conductance. Ba2+ and quinidine, whi ch are known to inhibit K+ channels in epithelia, prevented RVD. Addit ion of the K+ ionophore valinomycin (1 muM) caused follicle shrinkage that was prevented by phenamil (1 muM). We conclude that cultured foll icles respond to hypotonically induced stretch by activating outwardly directed Na+ transport through a mechanism which involves change in t he basolateral K+ conductance. This response would be characteristic o f a system that controlled follicle volume. However, it is not clear f rom these studies whether the cells responded primarily to the increas e in follicle volume or to the change in cell volume that is expected to accompany hypotonic challenge.