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Am J Physiol Cell Physiol 275: C515-C526, 1998;
0363-6143/98 $5.00
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Vol. 275, Issue 2, C515-C526, August 1998

Human cytomegalovirus infection stimulates Clminus /HCOminus 3 exchanger activity in human fibroblasts

Lilia M. Maglova, William E. Crowe, Aníbal A. Altamirano, and John M. Russell

Department of Physiology, Allegheny University of the Health Sciences, Philadelphia, Pennsylvania 19129

The effects of human cytomegalovirus (HCMV) infection on Cl-/HCO-3 exchanger activity in human lung fibroblasts (MRC-5 cells) were studied using fluorescent, ion-sensitive dyes. The intracellular pH (pHi) of mock- and HCMV-infected cells bathed in a solution containing 5% CO2-25 mM HCO-3 were nearly the same. However, replacement of external Cl- with gluconate caused an H2DIDS-inhibitable (100 µM) increase in the pHi of HCMV-infected cells but not in mock-infected cells. Continuous exposure to hyperosmotic external media containing CO2/HCO-3 caused the pHi of both cell types to increase. The pHi remained elevated in mock-infected cells. However, in HCMV-infected cells, the pHi peaked and then recovered toward control values. This pHi recovery phase was completely blocked by 100 µM H2DIDS. In the presence of CO2/HCO-3, there was an H2DIDS-sensitive component of net Cl- efflux (external Cl- was substituted with gluconate) that was less in mock- than in HCMV-infected cells. When nitrate was substituted for external Cl- (in the nominal absence of CO2/HCO-3), the H2DIDS-sensitive net Cl- efflux was much greater from HCMV- than from mock-infected cells. In mock-infected cells, H2DIDS-sensitive, net Cl- efflux decreased as pHi increased, whereas for HCMV-infected cells, efflux increased as pHi increased. All these results are consistent with an HCMV-induced enhancement of Cl-/HCO-3 exchanger activity.

cell volume; hydrogen 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid; sodium/hydrogen exchanger


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