Calcium modulation and cell injury in isolated rat proximal tubules.
The possible role of an increased calcium influx in mediating hypoxia-induced injury in isolated rat proximal tubules was examined. Reduction of extracellular calcium delayed the development of proximal tubule cell injury as reflected by the release of lactate dehydrogenase (LDH). This protection, as assessed by LDH release, was not associated with improvements of cell ATP or potassium concentrations. The calcium channel blocker verapamil also delayed the development of cell injury due to hypoxia. This protective effect was evident in the presence of normal or low extracellular calcium. Specifically, hypoxic tubules incubated in low calcium medium were further protected by the addition of verapamil. The protection with verapamil was evident not only by diminished LDH release, but also by improvements in cell ATP and potassium concentration. Further experiments demonstrated that verapamil also increased cell potassium levels in control oxygenated tubules incubated in normal calcium medium. Thus, the results demonstrate that low calcium medium delays the onset of cell membrane injury during hypoxia as assessed by LDH release. The protective effects of verapamil can be demonstrated in the presence of normal or low calcium media, and involve not only diminished LDH release but also increased cell ATP and potassium concentrations. Therefore, in addition to any effect on calcium influx, the effect of verapamil appears to involve a protective effect at cell membrane or mitochondria sites.
Wetzels
J F
JF
Department of Medicine, University of Colorado School of Medicine, Denver.
Yu
L
L
Wang
X
X
Kribben
A
A
Burke
T J
TJ
Schrier
R W
RW
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000502:physiology*; D002463:Cell Membrane Permeability; D002470:Cell Survival; D000860:Hypoxia / Q000503:physiopathology*; D066298:In Vitro Techniques; D007687:Kidney Tubules, Proximal / Q000503:physiopathology*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D011188:Potassium / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014700:Verapamil / Q000494:pharmacology
D000255:Adenosine Triphosphate; D014700:Verapamil; D007770:L-Lactate Dehydrogenase; D011188:Potassium; D002118:Calcium