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. Reductio n 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 cha nnel blocker verapamil also delayed the development of cell injury due to hypoxia. This protective effect was evident in the presence of nor mal or low extracellular calcium. Specifically, hypoxic tubules incuba ted in low calcium medium were further protected by the addition of ve rapamil. The protection with verapamil was evident not only by diminis hed LDH release, but also by improvements in cell ATP and potassium co ncentration. Further experiments demonstrated that verapamil also incr eased 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 ass essed by LDH release. The protective effects of verapamil can be demon strated in the presence of normal or low calcium media, and involve no t only diminished LDH release but also increased cell ATP and potassiu m concentrations. Therefore, in addition to any effect on calcium infl ux, the effect of verapamil appears to involve a protective effect at cell membrane or mitochondria sites.