Impaired renal calcium absorption in mice lacking calcium channel beta 3 subunits.
Transgenic mice lacking calcium channel beta3 subunits (CaVbeta3) were used to determine the involvement of a multimeric calcium channel in mediating stimulated renal calcium absorption. We measured the ability of calcium channel beta3 subunit-null (CaVbeta3-/-) and wild-type (CaVbeta3+/+) mice to increase renal calcium absorption in response to the calcium-sparing diuretic chlorothiazide (CTZ). Control rates of fractional sodium excretion were comparable in CaVbeta3-/- and CaVbeta3+/+ mice and CTZ increased sodium excretion similarly in both groups. CTZ enhanced calcium absorption only in wild-type CaVbeta3+/+ mice. This effect was specific for diuretics acting on distal tubules because both CaVbeta3-/- and CaVbeta3+/+ mice responded comparably to furosemide. The absence of beta3 subunits resulted in compensatory increases of TrpV5 calcium channels, the plasma membrane Ca-ATPase, NCX1 Na/Ca exchanger protein, and calbindin-D9k but not calbindin-D28k. We conclude that TrpV5 mediates basal renal calcium absorption and that a multimeric calcium channel that includes CaVbeta3 mediates stimulated calcium transport.
Bernardo
José F
JF
Department of Medicine, Renal Electrolyte Division, W1340 Biomedical Science Tower, Pittsburgh, PA 15261, USA.
Magyar
Clara E
CE
Sneddon
W Bruce
WB
Friedman
Peter A
PA
D000042:Absorption / Q000235:genetics; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000172:deficiency* / Q000235:genetics* / Q000502:physiology; D007668:Kidney / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D021381:Protein Transport / Q000235:genetics; D050916:TRPV Cation Channels / Q000502:physiology
C510225:Cacnb3 protein, mouse; D015220:Calcium Channels; D050916:TRPV Cation Channels; C492240:Trpv5 protein, mouse; D002118:Calcium