Functional significance of K+ and Cl- channels in volume regulation in proximal tubular cells.

Using the patch-clamp technique to cultured opossum kidney (OK) cells, we measured the activities of K+ channel and Cl- conductance during hyposmotic stress. The results are as follows: 1) A 50% lowered osmolarity of bath media induced a biphasic change of the membrane potential (EM): early hyperpolarization and late depolarization. The former transient response was abolished by removing Ca2+ from the cellular media, whereas the latter slow response was blocked by DIDS. 2) The hyposmosis-induced change of EM was due to K+ channels activated by cytosolic Ca2+. 3) In hyposmotic media, Cl- current was effectively increased, and this effect was abolished by Cl- channel blockers. 4) The hyposmosis-induced Cl- conductance was inhibited in the cytosolic acid media. In the alkaline media, it was enhanced even without hyposmotic stress. We conclude that the hyposmosis-induced activation of Cl- conductance, being stimulated by alkaline cell pH and inhibited by acid cell pH, may contribute to the ion transport and cell volume regulation along with the Ca(2+)-activated K+ channel.