Transient potassium conductances protect nucleus tractus solitarius neurons from NMDA induced excitotoxic plateau depolarizations
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Ischemic insults, followed by excessive accumulation of extracellular glutamate, destroy most, but not all, neurons in affected area(s) of the central nervous system (CNS). Characterization of the unique properties of cells resistant to such excitotoxic challenge may identify novel preventive/therapeutic strategies to reduce cell death. We have previously reported that transient potassium conductances expressed in magnocellular neurons of the paraventricular nucleus protect these cells from excitotoxic cell death. In the present study, in vitro patch-clamp recording techniques were used to assess the roles of similar potassium conductances in protecting delayed excitation (DE) neurons of the nucleus tractus solitarius (NTS) from over-excitation after N-methyl-d-aspartate (NMDA) receptor activation. DE neurons show a reduced sensitivity (compared to NTS neurons which lack these potassium conductances) to NMDA receptor activation which protects against long duration plateau depolarizations (LDPDs). We identify two types of transient K(+) conductances (I(A) and I(D)), which contribute to the rapid repolarization of the membrane after a strong depolarization, and show that inhibition of these currents with 4-aminopyridine increases neuronal excitability after NMDA receptor activation such that DE cells now respond with LDPDs. In contrast, lower concentrations of 4-AP (100 mM) which inhibit only the I(D) have no effect on NMDA induced depolarization. These results suggest that the reduced sensitivity of DE neurons in NTS to NMDA receptor activation is the result of the large transient potassium conductance I(A) expressed in these neurons, and identify this as a common mechanism protecting against NMDA receptor mediated excitotoxicity in both PVN and NTS neurons.
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