title: Volume-activated calcium uptake: its role in cell volume regulation of Madin-Darby canine kidney cells.
abstract: Immediately after osmotic swelling of Madin-Darby canine kidney (MDCK) cells, a transient (1-2 min) increase in Ca2+ influx and internal Ca2+ (Ca2+i) is observed. The normal Ca2+ influx appears to be mediated by the 3Na(+)-Ca2+ exchange system [Borle et al. Am. J. Physiol. 259 (Cell Physiol. 28): C19-C25, 1990], but the swelling-induced component is different in 1) Na+ dependence, 2) affinity for Ca2+, 3) inhibition by La3+, and 4) direction of net flux at low external Ca2+. Swelling appears to activate an uncoupled Ca2+ flow, perhaps through cation-nonspecific stretch-activated channels. The regulatory volume decrease (RVD) is dependent on the swelling-induced pulse of Ca2+ influx and associated rise in Ca2+i. Swelling also induces a biphasic change in membrane potential, a hyperpolarization followed by depolarization, reflecting sequential increases in K+ and Cl- permeabilities. The time dependence of the former corresponds closely with the transient peak in Ca2+i, but the latter does not. Ca2+i appears to have a direct activating effect on K+ channels but an indirect effect on Cl- channels, mediated via other Ca(2+)-triggered systems. The sequence of events following cell swelling appears to be transient increases in Ca2+ permeability, Ca2+ influx, Ca2+i, K+ permeability, followed by triggering of a mediating system that increases Cl- permeability. The net result is KCl, osmotic water loss, and volume adjustment.
authors.affiliation: Research Institute, Hospital for Sick Children, Toronto, Ontario, Canada.
authors.forename: A
authors.initials: A
authors.lastname: Rothstein
authors.forename: E
authors.initials: E
authors.lastname: Mack
mesh_terms: D000818:Animals; D002118:Calcium / Q000493:pharmacokinetics*; D002460:Cell Line; D002463:Cell Membrane Permeability; D002712:Chlorides / Q000493:pharmacokinetics; D004285:Dogs; D007668:Kidney / Q000166:cytology / Q000378:metabolism* / Q000502:physiology; D008564:Membrane Potentials; D011188:Potassium / Q000493:pharmacokinetics
chemical_list: D002712:Chlorides; D011188:Potassium; D002118:Calcium