生体膜輸送の新たなる展開 消化管上皮細胞の容積調節機構：Ｃｌチャネルの役割

Abstract

Cell volume regulation under osmotic stress is one of the important cell functions to maintain cell homeostasis. Absorptive intestinal epithelial cells are obliged to swell in association with active absorption of nutrients, whereas secretory cells in the intestinal crypt exhibit shrinkage due to Na+ and H2O secretion driven by active Cl- secretion. After osmotic swelling and shrinkage, intestinal epithelial cells undergo a regulatory volume decrease (RVD) or a regulatory volume increase (RVI), respectively, to restore their original volume. In human epithelial Intestine 407 cells, we demonstrated that the RVD is accomplished by parallel activation of Ca2+-activated K+ channel (IK1) and volume-sensitive outwardly rectifying Cl- channel (VSOR). Small intestinal and colonic epithelial cells have been reported to respond with shrinkage to secretagogue stimulation. We utilized a human colonic epithelial cell line, T84, as a model to clarify the ion transport mechanisms of volume responses to secretagogue situmulation. T84 cells exhibited shrinkage, called a secretory volume decrease (SVD), after stimulation with carbachol (CCh), and they thereafter restored their original volume even during CCh stimulation. Our data showed that CCh-induced SVD is induced by Cl- secretion via Ca2+-activated Cl- channels, and, on the other hand, the succeeding RVI is by NaCl uptake via Na+-K+-2Cl- cotransporters (NKCC). These findings indicate that when intestinal cells are faced with osmotic stress, which is inevitably coupled to active absorption and secretion, they can regulate their volume by activating ion channels and/or transporters.