Control of neuronal excitability by an ion-sensing receptor (correction of anion-sensing)

摘要: While most central nervous system (CNS) neurons receive the majority of their input through direct synaptic connections, there is evidence suggesting that they are in fact susceptible to modulation by changes extracellular ionic composition during both physiological and pathophysiological conditions. In many regions CNS, exists an identified receptor with ability sense levels cations, notably calcium. Here we report activation this calcium (CaR) subfornical organ (SFO), a forebrain circumventricular structure, results profound effects on neuronal excitability metabotropic actions non-selective cation channel. Activation CaR NPS R-467, allosteric agonist CaR, evoked depolarizing plateau potentials ranging duration from 5 30 s. Similarly, mm CaCl2 caused depolarization increased action potential frequency. R-467 was found activate channel reversal -48 +/- 4 mV, slope conductance 2.54 11 nS. This current could also be elicited spermine, known CaR. CaR-mediated dependent upon G proteins intracellular Ca2+ signalling, as disruption these pathways inclusion guanosine 5'-O-(2-thiodiphosphate) (GDP-beta-S) 1,2-bis(2-aminophenoxy)ethane-N,N,N ',N '-tetraacetic acid (BAPTA), respectively, recording pipette prevented current. Microinjection agonists into SFO anaesthetized rats resulted significant, site-specific elevation blood pressure (mean area under curve, 141 50 mmHg. s). Together, indicate can play important role transducing composition, have implications for neural control fluid balance.