MODULATION BY POLYCATIONIC CA2-SENSING RECEPTOR AGONISTS OF NONSELECTIVE CATION CHANNELS IN RAT HIPPOCAMPAL-NEURONS()

We recently cloned an extracellular calcium (Ca-0(2+))-sensing recepto r (CaR) from bovine parathyroid. The CaR is also expressed in various regions of brain, suggesting that it could potentially mediate some of the well-known but poorly understood effects of Ca-0(2+) on neuronal function. We have now examined the effects of polycationic CaR agonist s on the activity of nonselective cation channels (NCC) in cultured ra t hippocampal neurons, using the cell-attached configuration of the pa tch clamp technique and applying CaR active agents to the external bat h solution. The polycationic CaR agonist, neomycin (100 mu M), as well as an elevated concentration of Ca-0(2+) (3 mM), which is known to ac tivate the cloned CaR, significantly increased the probability of chan nel opening (Po). The polyamine, spermine (300 mu M), which also mimic s the actions of Ca-0(2+) on the cloned CaR, produced similar changes in Po in rat hippocampal neurons. Elevation of Ca-0(2+) also increased Po for a similar NCC in HEK293 cells transfected with the cloned huma n CaR but not in nontransfected HEK cells. Thus the CaR can regulate t he activity of Ca2+-permeable NCC in hippocampal neurons and could pot entially modulate key functions of these cells, including neurotransmi ssion and neuronal excitability. (C) 1996 Academic Press, Inc.