title: Hypoxia decreases calcium influx into rat proximal tubules.
abstract: Renal ischemia results in adenosine triphosphate (ATP) depletion, particularly in cells of the proximal tubule (PT), which rely heavily on oxidative phosphorylation for energy supply. Lack of ATP leads to a disturbance in intracellular homeostasis of Na+, K+ and Cl-. Also, cytosolic Ca2+ levels in renal PTs may increase during hypoxia [1], presumably by a combination of impaired extrusion and enhanced influx [2]. However, Ca2+ influx was previously measured using radiolabeled Ca2+ and at varying partial oxygen tension [2]. We have now used to Mn2(+)-induced quenching of fura-2 fluorescence to study Ca2+ influx in individual rat PTs during normoxic and hypoxic superfusion. Normoxic Ca2+ influx was indeed reflected by the Mn2+ quenching of fura-2 fluorescence and this influx could be inhibited by the calcium entry blocker methoxyverapamil (D600; inhibition 50 +/- 2% and 35 +/- 3% for 10 and 100 mumol, respectively). La3+ completely blocked normoxic Ca2+ influx. Hypoxic superfusion or rat PTs did not induce an increase in Ca2+ influx, but reduced this influx to 79 +/- 3% of the normoxic control. We hypothesize that reducing Ca2+ influx during hypoxia provides the cell with a means to prevent cellular Ca2+ overload during ATP-depletion, where Ca2+ extrusion is limited.
authors.affiliation: Department of Cell Physiology, University of Nijmegen, The Netherlands.
authors.forename: S M
authors.initials: SM
authors.lastname: Peters
authors.forename: M J
authors.initials: MJ
authors.lastname: Tijsen
authors.forename: C H
authors.initials: CH
authors.lastname: van Os
authors.forename: J F
authors.initials: JF
authors.lastname: Wetzels
authors.forename: R J
authors.initials: RJ
authors.lastname: Bindels
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D005246:Feedback; D005456:Fluorescent Dyes; D016257:Fura-2; D005711:Gallopamil / Q000494:pharmacology; D006706:Homeostasis; D000860:Hypoxia / Q000378:metabolism*; D066298:In Vitro Techniques; D017136:Ion Transport / Q000187:drug effects; D007687:Kidney Tubules, Proximal / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008345:Manganese / Q000378:metabolism; D009243:NAD / Q000378:metabolism; D010477:Perfusion; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D002121:Calcium Channel Blockers; D005456:Fluorescent Dyes; D009243:NAD; D005711:Gallopamil; D008345:Manganese; D000255:Adenosine Triphosphate; D002118:Calcium; D016257:Fura-2