PMID- 8570863 OWN - NLM STAT- MEDLINE DCOM- 19960301 LR - 20190515 IS - 0886-022X (Print) IS - 0886-022X (Linking) VI - 17 IP - 5 DP - 1995 Sep TI - Induced alterations in calcium uptake rate in normoxic rate proximal tubules. PG - 503-15 AB - This study is well-oxygenated, freshly isolated rat proximal tubules (RPT), examined the effects of several drugs that alter the transmembrane K+ and Na+ gradients across cell membranes, including valinomycin (VAL), amphotericin B (AMPHO), and ouabain (OUAB). The effects of high extracellular potassium chloride (KCl) concentrations (45 mM) and low extracellular sodium concentration (100mM) were also studied. After 10 min of drug exposure Ca2+ uptake rate (nmol/mg/min) increased from 2.7 to 3.8 with VAL (p < .02), from 2.9 to 3.7 with AMPHO (p < .05), from 3.6 to 4.1 with OUAB (p < .05), and from 3.2 to 4.8 with 45 mM KCl (p < .001). Ca2+ uptake rate was sustained at these high levels at 20 min in all treated RPT except those exposed to OUAB. LDH release averaged less than 15% in control tubules and did not increase significantly except in RPT treated with VAL, where LDH release at 10 min was 48% and at 20 min was 57% (both p < .001). Of importance, only in VAL-treated RPT did ATP decrease to low levels (6.7 nmol/mg in control to 2.0 +/- 0.3 nmol/mg in VAL, p < .001). Treatment with verapamil reduced Ca2+ uptake rates at 10 min in VAL-treated RPT (from 3.8 to 3.1, p < .02, in AMPHO-treated RPT (from 3.8 to 3.1 p < .001), in OUAB-treated tubules (from 4.0 to 3.4, p < .01), and in KCl-treated RPT (from 3.7 to 3.2, p < .01). These results indicate that acute changes in the transmembrane ion gradient in RPT are accompanied by increased Ca2+ uptake rates. Ca2+ uptake rates are also increased during O2 deprivation in RPT, a situation in which the transmembrane ion gradient is likewise altered. The increased Ca2+ uptake rate observed in the present study and during hypoxia may have a common basis, that is, altered transmembrane ion gradients or some function thereof. FAU - Burke, T J AU - Burke TJ AD - Department of Medicine, University of Colorado School of Medicine, Denver 80262, USA. FAU - Joseph, J K AU - Joseph JK FAU - Bunnachak, D AU - Bunnachak D FAU - Almeida, A AU - Almeida A FAU - Wetzels, J F AU - Wetzels JF FAU - Yu, L AU - Yu L FAU - Kribben, A AU - Kribben A FAU - Wieder, E AU - Wieder E FAU - Schrier, R W AU - Schrier RW LA - eng GR - 35098/PHS HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. PL - England TA - Ren Fail JT - Renal failure JID - 8701128 RN - 0 (Ionophores) RN - 2001-95-8 (Valinomycin) RN - 5ACL011P69 (Ouabain) RN - 7XU7A7DROE (Amphotericin B) RN - 8L70Q75FXE (Adenosine Triphosphate) RN - 9NEZ333N27 (Sodium) RN - EC 1.1.1.27 (L-Lactate Dehydrogenase) RN - RWP5GA015D (Potassium) RN - SY7Q814VUP (Calcium) SB - IM MH - Adenosine Triphosphate/metabolism MH - Amphotericin B/pharmacology MH - Animals MH - Calcium/*metabolism MH - Cell Membrane Permeability/drug effects/*physiology MH - In Vitro Techniques MH - Ionophores/pharmacology MH - Kidney Tubules, Proximal/cytology/drug effects/*metabolism MH - L-Lactate Dehydrogenase/drug effects/metabolism MH - Male MH - Membrane Potentials/drug effects MH - Ouabain/pharmacology MH - Potassium/metabolism MH - Rats MH - Rats, Sprague-Dawley MH - Sodium/metabolism MH - Valinomycin/pharmacology EDAT- 1995/09/01 00:00 MHDA- 1995/09/01 00:01 CRDT- 1995/09/01 00:00 PHST- 1995/09/01 00:00 [pubmed] PHST- 1995/09/01 00:01 [medline] PHST- 1995/09/01 00:00 [entrez] AID - 10.3109/08860229509037615 [doi] PST - ppublish SO - Ren Fail. 1995 Sep;17(5):503-15. doi: 10.3109/08860229509037615.