title: The reduction of EPSC amplitude in CA1 pyramidal neurons by the peroxynitrite donor SIN-1 requires Ca2+ influx via postsynaptic non-L-type voltage gated calcium channels.
abstract: The peroxynitrite free radical (ONOO(-)) modulation of miniature excitatory postsynaptic currents (mEPSCs) and spontaneous excitatory postsynaptic currents (sEPSCs) was investigated in rat CA1 pyramidal neurons using the whole-cell patch clamp technique. SIN-1(3-morpholino-sydnonimine), which can lead the simultaneous generation of superoxide anion and nitric oxide, and then form the highly reactive species ONOO(-), induced dose-dependent inhibition in amplitudes of both mEPSCs and sEPSCs. The SIN-1 action on mEPSC amplitude was completely blocked by U0126, a selective MEK inhibitor, suggesting that MEK contributed to the action of ONOO(-) on mEPSCs. The effect of SIN-1 was completely occluded either in the presence of the calcium chelator EGTA or the non-selective calcium channel antagonist Cd(2+). Furthermore, the application of nifedipine (20 μM), the L-type calcium channel blocker, had no effect on the ONOO(-)-induced decrease in mEPSC amplitude, excluding a role for L-type voltage-gated Ca(2+) channels in this process. SIN-1 inhibited the frequency of sEPSCs but had no effect on mEPSC frequency, which suggested a presynaptic action potential-dependent the action of ONOO(-) at CA1 pyramidal neuron synapses. The best-known glutamatergic input to CA1 pyramidal neurons is via Schaffer collaterals from CA3 area. However, no changes were observed in slices treated with SIN-1 on the spontaneous firing rates of CA3 pyramidal neurons. These findings suggested that SIN-1 inhibited glutamatergic synaptic transmission of CA1 pyramidal neurons by a postsynaptic non-L-type voltage gated calcium channel-dependent mechanism.
authors.affiliation: College of Medicine, Nankai University, Tianjin, 300071, China.
authors.forename: Liu
authors.initials: L
authors.lastname: Zhaowei
authors.forename: Xie
authors.initials: X
authors.lastname: Yongling
authors.forename: Yang
authors.initials: Y
authors.lastname: Jiajia
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhuo
mesh_terms: D000818:Animals; D002070:Butadienes / Q000494:pharmacology; D056547:CA1 Region, Hippocampal / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000502:physiology*; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D017136:Ion Transport; D008297:Male; D008981:Molsidomine / Q000031:analogs & derivatives* / Q000494:pharmacology; D009570:Nitriles / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
chemical_list: D002070:Butadienes; D015220:Calcium Channels; D009570:Nitriles; C113580:U 0126; C002385:linsidomine; D008981:Molsidomine; D002118:Calcium