Cell shrinkage evoked by Ca super(2+)-free solution in rat alveolar type II cells: Ca super(2+) regulation of Na super(+)-H super(+) exchange

• Published in: Experimental physiology Vol. 90; no. 2; pp. 203 - 213
• Main Authors: Murao, Hitoshi, Shimizu, Akira, Hosoi, Keita, Iwagaki, Akitaka, Min, Kyong-Yob, Kishima, Gen-ichi, Hanafusa, Toshiaki, Kubota, Takahiro, Kato, Masumi, Yoshida, Hideyo, Nakahari, Takashi
• Format: Journal Article
• Language: English
• Published: 01.03.2005
• ISSN: 0958-0670; 1469-445X
• DOI: 10.1113/expphysiol.2004.028837

The effects of intracellular Ca super(2+) concentration, [Ca super(2+)] sub(i), on the volume of rat alveolar type II cells (AT-II cells) were examined. Perfusion with a Ca super(2+)-free solution induced shrinkage of the AT-II cell volume in the absence or presence of amiloride (1 mu m, an inhibitor of Na super(+) channels); however, it did not in the presence of 5-(N-methyl-N-isobutyl)-amiloride (MIA, an inhibitor of Na super(+)-H super(+) exchange). MIA decreased the volume of AT-II cells. Inhibitors of Cl super(-)-HCO sub(3) super(-) exchange, 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS) and 4-acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic acid (SITS) also decreased the volume of AT-II cells. This indicates that the cell shrinkage induced by a Ca super(2+)-free solution is caused by a decrease in NaCl influx via Na super(+)-H super(+) exchange and Cl super(-)-HCO sub(3) super(-) exchange. Addition of ionomycin (1 mu m), in contrast, induced cell swelling when AT-II cells were pretreated with quinine and amiloride. This swelling of the AT-II cells is not detected in the presence of MIA. Intracellular pH (pH sub(i)) measurements demonstrated that the Ca super(2+)-free solution or MIA decreases pH sub(i), and that ionomycin increases it. Ionomycin stimulated the pH sub(i) recovery after an acid loading (NH sub(4) super(+) pulse method), which was not noted in MIA-treated AT-II cells. Ionomycin increased [Ca super(2+)] sub(i) in fura-2-loaded AT-II cells. In conclusion, the Na super(+)-H super(+) exchange activities of AT-II cells, which maintain the volume and pH sub(i), are regulated by [Ca super(2+)] sub(i).