Hypoxia decreases calcium influx into rat proximal tubules.
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.
Peters
S M
SM
Department of Cell Physiology, University of Nijmegen, The Netherlands.
Tijsen
M J
MJ
van Os
C H
CH
Wetzels
J F
JF
Bindels
R J
RJ
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
D002121:Calcium Channel Blockers; D005456:Fluorescent Dyes; D009243:NAD; D005711:Gallopamil; D008345:Manganese; D000255:Adenosine Triphosphate; D002118:Calcium; D016257:Fura-2