The extracellular calcium-sensing receptor is expressed in rat microglia and modulates an outward K+ channel.
The calcium-sensing receptor (CaR) is a G protein-coupled receptor that "senses" extracellular calcium ions (Ca2+o) as an extracellular first messenger. In this report, we have shown that the CaR is expressed in primary cultures of microglial cells derived from rat brain as assessed by RT-PCR using four CaR-specific primer pairs followed by sequencing of the amplified products, by northern blot analysis using a CaR-specific probe, as well as by immunocytochemistry and western analysis utilizing a specific polyclonal anti-CaR antiserum. In addition, raising Ca2+o from 0.75 to 3.0 mM or addition of the polycationic CaR agonist neomycin or a "calcimimetic" CaR activator (R-467; NPS Pharmaceuticals) increased the open state probability (Po) of a Ca(+)-activated K+ channel having a unitary conductance of 84+/-4 pS, indicating that the channel is modulated by the CaR. Therefore, our data strongly suggest that a functional CaR is expressed in cultured rat microglia, similar to that in parathyroid gland and kidney, which could potentially play an important role(s) in regulating microglial function.
Chattopadhyay
N
N
Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.
Ye
C
C
Yamaguchi
T
T
Nakai
M
M
Kifor
O
O
Vassilev
P M
PM
Nishimura
R N
RN
Brown
E M
EM
D000818:Animals; D015415:Biomarkers; D015153:Blotting, Western; D002118:Calcium / Q000502:physiology; D005110:Extracellular Space / Q000378:metabolism*; D015870:Gene Expression / Q000502:physiology; D017628:Microglia / Q000378:metabolism* / Q000502:physiology; D015221:Potassium Channels / Q000378:metabolism*; D051381:Rats; D044169:Receptors, Calcium-Sensing; D011956:Receptors, Cell Surface / Q000819:agonists / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D015415:Biomarkers; D015221:Potassium Channels; D044169:Receptors, Calcium-Sensing; D011956:Receptors, Cell Surface; C473605:extracellular calcium cation-sensing receptor, rat; D002118:Calcium