Possible Interaction: 4-Aminopyridine and Gamma-Aminobutyric Acid

“Using whole-cell recordings from acute rat PAG slices, we report here that the bath application of 4-aminopyridine , a voltage-gated K+ channel blocker, increases the initial GABA and glutamate release probability (P) and reinstates P depressed by presynaptic GABAB receptor activation at inhibitory and excitatory synapses, respectively.”

“ 4-AP induced intense epileptic discharges, increased the extracellular levels of aspartate, glutamate, and GABA by 383, 420, and 245%, respectively, and produced a notable neurodegeneration in CA1 and CA3 areas.”

“At 200 microM, 4-AP inhibited postsynaptic GABA currents induced by 5 microM GABA to 68.2+/-15.5%: by countering the effect of enhanced release of GABA from presynaptic terminals, this could depress the inhibitory pathway.”

“ 4-Aminopyridine , which blocks K+-conductance of excitable membranes, reversibly abolished both the glial depolarization and the [K+]0 increase produced by GABA and glycine.”

“The experiments have shown that release of [3H]GABA evoked by the depolarization with 4-AP was decreased by 80% as a result of action of 3 microM PAO and the complete inhibition of release was observed with 10 microM PAO.”

“ 4-aminopyridine elicited high-frequency seizure discharges in the EEG and significantly increased glutamate, aspartate, GABA , serotonin, noradrenaline, and dopamine levels in the extracellular dialysates.”

“This developmental upregulation was paralleled by a dramatic increase in total K+current, as well as an elevated GABA release in the presence of 4-aminopyridine.”

“Perfusion with 20-75 mM 4-AP for 12.5 min resulted in a massive increase in extracellular glutamate (up to 20-fold), smaller increases in aspartate and taurine (up to 10-fold) and slight increments in glutamine, alanine, glycine and GABA.”

“ 4-Aminopyridine had a minimal effect on total tissue concentrations of glutamate, aspartate, and GABA , but caused a significant increase in their de novo synthesis.”

“The increases in dorsal root fiber responses produced by GABA were depressed by tetraethylammonium (TEA) (3 mM), 4-aminopyridine (4-AP) (50 microM), Cs (2 mM), and Ba (1 mM).”