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5b (novel blocker of ASICs) has reebok look little effect on inward GABAergic currents in  HEPES 10' solution. In the same series of experiments during each sweep evoked PSCs were recorded below their reversal potential as inward currents ( a ), and above the reversal potential, as outward ones ( b ). Superimposed traces of original current traces (averages of 10 sequential PSCs) before (solid lines) and after (dotted lines) 5b (1 ¼M) application are shown on the right panel, summary graphs ( n = 5) are shown on the left panel. PSC-amplitudes were normalized to control values (average of 20 PSCs preceding drug application).

On the other hand, direct involvement 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 reebok classic 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 reebok shoes did observe a decrease of the inward currents and a small decrease in the outward currents.

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 reebok the pump 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.

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.

It is worth noting that feature of voltage-dependence of interaction between receptors is, of itself, not very surprising. Indeed, a physical link between group-I metabotropic glutamate receptors and NMDA receptors results in a functional crosstalk, which is voltage-dependent [ 39 ]. Nevertheless we cannot currently exclude a possibility that the modulation of PSCs by ASICs under our experimental conditions depends on the direction of the current, rather than being intrinsically voltage-dependent. This, however, is less likely because in isolated reebok pump neurons the interaction of ASICs and GABAA receptors does not depend on the direction of the GABA-current [ 10 ].

ASICs are abundant in many brain areas and are known to have important physiological functions. However, because of rapid desensitization of ASIC-mediated currents, synapses are among the few places where they can be activated under physiological conditions and, thus, mediate their physiological roles. In this work we demonstrated for the first time that three structurally different ASIC blockers affect GABAergic PSCS in a similar manner, strongly suggesting that ASICs are involved in regulation of GABAegic synaptic transmission under physiological conditions.