Calcium handling by renal tubules during oxygen deprivation injury to the kidney prior to reoxygenation.

Efforts to more precisely define the mechanism(s) of ischemic injury to renal epithelial tissue, both during O2 deprivation and reflow, have led to the expanding use of freshly isolated renal tubules. This tissue is prepared in a manner that eliminates the impact of changes in vascular resistance and influences of hormones, as well as temporal changes in pH and in regional pO2, and has permitted investigators to focus on the definitive cellular responses to O2 deprivation itself. When such studies are evaluated it becomes clear that in vitro anoxia, for up to 60 minutes, is not associated with any increase in total tissue Ca2+ as measured by atomic absorption techniques, whereas severe hypoxia is attended by a time-dependent increase in total tissue Ca2+. In both severe hypoxia and anoxia, however, the Ca2+ uptake rate is increased, but during hypoxia the less severe acidosis, as well as the continued, albeit modest, mitochondrial energization, appears to facilitate mitochondrial (and thus total tissue) Ca2+ accumulation. In vivo and in vitro, the administration of calcium channel blockers (CCB) attenuates renal oxygen-deprivation-induced injury and one, often overlooked, effect of verapamil, a prototypical CCB, is to reduce K+ loss from treated tissue via inhibition of Ca2(+)-mediated K+ efflux pathways. This may be the cause of the higher levels of K+ reported for several tissues, including kidney tubules, during CCB treatment. In addition, reduced rates of Ca2+ uptake effected by CCB may modify cytosolic free Ca2+ levels such that activation of phospholipases is impaired.(ABSTRACT TRUNCATED AT 250 WORDS)