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Philip Trollpoe
Kognik
Dołączył: 25 Mar 2020 Posty: 3
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On the other hand, direct involvement asics look of ASICs in PSCs generation documented for lateral amygdala neurons [ 5 ], does not seemingly occur in hippocampal neurons [ 6 , 36 ]. Our results tend to agree with the latter observations. Indeed, under our experimental conditions, if a substantial fraction of synaptic current is mediated by ASICs, a decrease in the net inward current, and an increase in the net outward current would be expected once ASICs are blocked. While in the presence of ASIC antagonists we did observe a decrease of the inward currents and a small decrease in the outward currents.
Since the density of proton-activated currents (evoked by pH shift to 5) is ~ 75 pA/pF in amygdala and 20 pA/pF in hippocampus [ 8 ], a much reduced proton-mediated component of synaptic current in the hippocampus may be expected. In our experiments, however, the asics shoes absolute value of inward synaptic current suppressed by ASIC antagonists is about 40 60 pA. As for the current 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 asics gel 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 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 asics gel s DRG neurons [ 11 ]. These data suggest direct protein-protein mechanism of interaction between GABA A and ASICs.
This suggestion is also indirectly supported by the observation that modulatory effect of GABA A -receptors activation on ASICs-currents can be observed in excised patches [ 10 ]. We assume that an interaction between ASICs and GABA A -receptors is quite likely to occur at GABAergic synapses upon acidification at the synaptic cleft. This assumption can be supported by the lack of the apparent effect of 5b on inward PSCS in the presence of bicuculline, observed in our experiments.
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 asics gel kayano activation of ASICs [ 11 ] may be not just a coincidence.
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Sro Mar 25, 2020 09:18 |
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Sro Mar 25, 2020 09:18 |
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