Evidence for a calcium-sensing receptor in the vascular smooth muscle cells of the spiral modiolar artery

J Membr Biol. 2000 Jun 1;175(3):203-12. doi: 10.1007/s00232001068.

Abstract

The vascular diameter of the gerbilline spiral modiolar artery has been shown to depend on the presence of extracellular Ca(2+) but it remained unknown whether the smooth muscle cells of this arteriole contain a Ca(2+) sensing receptor (CaSR). The cytosolic Ca(2+) concentration ([Ca(2+)](i)) was monitored as fluo 3 fluorescence and the vascular diameter was measured by video-microscopy in isolated in vitro superfused spiral modiolar arteries. RT-PCR was used to probe for the presence of CaSR transcripts. Increasing the extracellular Ca(2+) concentration ([Ca(2+)](o)) from 1 to 10 mm caused a biphasic increase in [Ca(2+)](i) that was paralleled by a vasoconstriction. The initial rate of this vasoconstriction, 2.01 +/- 0.07 microm/sec (n = 131), was inhibited when cytosolic Ca(2+) stores were presumably depleted with thapsigargin (IC(50) = 3 x 10(-9) m, n = 26) or ryanodine (IC(50) = 4 x 10(-8) m, n = 25) or when PLC was inhibited by 10(-6) m U73122 (n = 8). The initial rate of this constriction was not affected by the L-type Ca(2+) channel blocker 10(-6) m nifedipine (n = 5), by 10(-6) m U73343 (n = 6), which is the inactive analogue of U73122, by the T-type Ca(2+) channel blocker 10(-6) Gd(3+) (n = 6) or the Na(+)/Ca(2+) exchanger blocker 10(-4) m Ni(2+) (n = 5). The agonist rank potency order was Gd(3+) > Ni(2+) > Ca(2+) >> neomycin = Mg(2+). Analysis of RNA isolated from the SMA revealed a RT-PCR product of the appropriate size for the CaSR (448 bp). Sequence analysis of the amplified cDNA fragment revealed a 94-96% amino acid identity compared to other CaSRs. These results demonstrate that the spiral modiolar artery contains a CaSR, which is most likely located in the vascular smooth muscle cells.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Arteries / cytology
  • Arteries / drug effects
  • Arteries / metabolism
  • Arteries / physiology
  • Base Sequence
  • Calcium / metabolism*
  • Calcium Channel Blockers / pharmacology
  • Cations, Divalent
  • Cochlea / blood supply
  • DNA, Complementary
  • Enzyme Inhibitors / pharmacology
  • Estrenes / pharmacology
  • Molecular Sequence Data
  • Muscle, Smooth, Vascular / cytology
  • Muscle, Smooth, Vascular / metabolism*
  • Muscle, Smooth, Vascular / physiology
  • Nickel / pharmacology
  • Nifedipine / pharmacology
  • Pyrrolidinones / pharmacology
  • Receptors, Calcium-Sensing
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / metabolism*
  • Ryanodine / pharmacology
  • Thapsigargin / pharmacology
  • Type C Phospholipases / antagonists & inhibitors
  • Vasodilator Agents / pharmacology

Substances

  • Calcium Channel Blockers
  • Cations, Divalent
  • DNA, Complementary
  • Enzyme Inhibitors
  • Estrenes
  • Pyrrolidinones
  • Receptors, Calcium-Sensing
  • Receptors, Cell Surface
  • Vasodilator Agents
  • 1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione
  • U 73343
  • Ryanodine
  • Thapsigargin
  • Nickel
  • Type C Phospholipases
  • Nifedipine
  • Calcium

Associated data

  • GENBANK/AF221064