Attenuation of glutamate-action, excitatory postsynaptic potentials, and spikes by intracellular QX 222 in hippocampal neurons

摘要: The effects of intracellular applications QX 222, a quaternary analogue lidocaine, were investigated in CA1 neurons vitro hippocampal slices guinea-pig brain. 222 produced strong depression spontaneous, electrically- (by current injection) or orthodromically-evoked action potentials. These dose-dependent characterized by reduction the rate rise and amplitude spikes, presumed to be mediated Na+-conductance. Although resting membrane conductance tended diminish with prolonged marked changes potential generally not observed. threshold for eliciting spikes injection depolarizing was increased greatly reflecting impairment Na+ -electrogenesis spikes. may partly attributable enhanced inactivation Na+-channels because brief pulses preceded tonic hyperpolarization, elicited at lower considerably larger than absence such hyperpolarization. observations on recovery are compatible removal sodium inactivation. However, this experimental paradigm also might expected remove molecules from their blocking sites inner end Na+-channels. When abolished depolarization evoked application S-glutamate pressure ejection an extracellular micropipette positioned close neuron attenuated. This reversible blockade reproducible 14 where interactions glutamate examined systematically. Excitatory postsynaptic potentials, stimulation strata oriens radiatum, reduced similar manner internal 222. These data confirm previous that voltage-dependent mediating spike genesis can blocked 222. apparently interferes functions -channels activated glutamate-receptor interaction receptor neurotransmitter(s) associated certain excitatory potentials neurons.