Ca-o-sensing receptor (CaR)-mediated activation of K+ channels is blunted in CaR gene-deficient mouse neurons

The extracellular Ca2+ (Ca-o)-sensing receptor (CaR) is expressed in hippocampus and other brain regions, suggesting that it could mediate some of the well recognized but poorly understood direct actions of Ca-o on neuronal function. This study presents evidence that the CaR is functionally coupled to Ca2+-activated K+ channels. The effects of CaR agonists on these channels in neurons from wild type (WT) and CaR-deficient (CaR -/-) mice were compared. Neomycin (100 mM) and elevation of Ca-o from 0.5 to 3 mM significantly increased the probability of channel opening (Po) in neurons from WT but not in those from CaR -/- mice. Thus the CaR activates neuronal K+ channels and could potentially inhibit neuronal excitability and neurotransmission via membrane repolarization.