Cell shrinkage evoked by Ca2+-free solution in rat alveolar type II cells: Ca2+ regulation of Na+-H+ exchange.
The effects of intracellular Ca2+ concentration, [Ca2+]i, on the volume of rat alveolar type II cells (AT-II cells) were examined. Perfusion with a Ca2+-free solution induced shrinkage of the AT-II cell volume in the absence or presence of amiloride (1 microm, an inhibitor of Na+ channels); however, it did not in the presence of 5-(N-methyl-N-isobutyl)-amiloride (MIA, an inhibitor of Na+-H+ exchange). MIA decreased the volume of AT-II cells. Inhibitors of Cl(-)-HCO3- 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 Ca2+-free solution is caused by a decrease in NaCl influx via Na+-H+ exchange and Cl(-)-HCO3- exchange. Addition of ionomycin (1 microm), 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 (pHi) measurements demonstrated that the Ca2+-free solution or MIA decreases pHi, and that ionomycin increases it. Ionomycin stimulated the pHi recovery after an acid loading (NH4+ pulse method), which was not noted in MIA-treated AT-II cells. Ionomycin increased [Ca2+]i in fura-2-loaded AT-II cells. In conclusion, the Na+-H+ exchange activities of AT-II cells, which maintain the volume and pHi, are regulated by [Ca2+]i.
Murao
Hitoshi
H
Central Clinical Laboratory, Osaka Medical College, Takatsuki, 569-8686, Japan.
Shimizu
Akira
A
Hosoi
Keita
K
Iwagaki
Akitaka
A
Min
Kyong-Yob
KY
Kishima
Gen-ichi
G
Hanafusa
Toshiaki
T
Kubota
Takahiro
T
Kato
Masumi
M
Yoshida
Hideyo
H
Nakahari
Takashi
T
D000818:Animals; D001693:Biological Transport, Active / Q000502:physiology; D002118:Calcium / Q000378:metabolism*; D048429:Cell Size; D002478:Cells, Cultured; D006706:Homeostasis / Q000502:physiology; D006863:Hydrogen-Ion Concentration; D008297:Male; D011650:Pulmonary Alveoli / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D012965:Sodium Chloride / Q000378:metabolism*; D017923:Sodium-Hydrogen Exchangers / Q000502:physiology*; D014882:Water-Electrolyte Balance / Q000502:physiology*
D017923:Sodium-Hydrogen Exchangers; D012965:Sodium Chloride; D002118:Calcium