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EdGabriel Offline



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Sat Mar 21, 2020 9:47 am
converse shoes Quote · reply

Since suramin (500 ¼M) does not affect ASIC currents in hippocampal converse shoes neurons [ 24 ] the above results also indicate that relative contribution of  synaptic' ASIC current is much smaller than 9 %. At the same time, the relative magnitude of the effects produced by ASIC blockers on synaptic currents recorded in the absence of bicuculline is about 20-30 %. These results, taken together, strongly support our point that the suppressing effect of the ASICs blockers on GABAergic transmission is due, predominantly to a modulatory mechanism. Additionally, we would like to mention that absolute amplitude of proton-mediated synaptic currents in amygdala is about 7-10 pA [ 5 ].

Since the density of proton-activated currents (evoked by pH shift to 5) is ~ 75 pA/pF in amygdala and 20 pA/pF in converse cdg hippocampus [ 8 ], a much reduced proton-mediated component of synaptic current in the hippocampus may be expected. In our experiments, however, the absolute value of inward synaptic current suppressed by ASIC antagonists is about 40 60 pA. As for the current converse hi tops mediated by ASICs in hippocampal GABAergic synapses, we believe this was undetectable due to its small absolute and relative amplitude.Functional interaction between ASICs and GABA A -receptors in isolated neurons has been recently demonstrated [ 10 , 11 ].

Activation of GABA A -receptors strongly changed ASIC-currents amplitude and pharmacological sensitivity [ 10 ], and the effect was blocked by antagonists of GABA A receptors [ 10 ]. On the other hand, a modulatory effect of ASIC activation on GABA A -currents was also observed converse c d g in HEK293 cells co-transfected with GABA A and ASIC1a or in primary cultured DRG neurons. The immunoassays showed that both GABA A and ASIC1a proteins were co-immunoprecipitated mutually either in HEK293 cells co-transfected with GABA A and ASIC1a or in primary cultured DRG neurons [ 11 ]. These data suggest direct protein-protein mechanism of interaction between GABA A and ASICs.

Indeed, this should be expected if the effect of 5b on inward PSCS in the absence of bicuculline is due to crosstalk between ASICs and GABA A -receptors, because the crosstalk in isolated neurons was blocked by antagonists of GABA A -receptors- receptors bicuculline and picrotoxin [ 10 ].Within the framework of this assumption, differential effects of the ASICs antagonists on inward and outward PSCs which we observed in our experiments would indicate that this interaction is voltage-dependent. In this regard, possibility to alter GABA-currents decay by changing voltage [ 37 , 38 ] and cdg converse activation of ASICs [ 11 ] may be not just a coincidence.

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