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In spite of the fact that the first evidence indicating asics look the presence of receptor for protons in the nerve cell membrane was obtained a long time ago [ 28 ] and tremendous progress in this field has been demonstrated in the subsequent studies [ 5 , 9 , 16 , 29  32 ] the physiological role of ASICs is still far from being clear. Their involvement in regulation and plasticity of glutamatergic synaptic transmission in the hippocampus has been demonstrated. Protons are considered to be neurotransmitters regulating synaptic plasticity in the lateral amygdala [ 5 ].

In spite of growing evidence indicating that the density of ASICs is substantially higher in GABAergic interneurons than in glutamatergic cells [ 17 ] and recent demonstration of functional crosstalk between ASICs and GABA A -receptors [ 10 , 11 ], the asics shoes possible involvement of ASICs in the regulation of GABAergic transmission remained unclear. In our work we present evidence for the first time that ASICs play a functional role at hippocampal GABAergic synapses. This role is mediated, at least partially, by a postsynaptic but (predominantly) modulatory mechanism.We asics gel found that GABAergic postsynaptic currents, recorded below their reversal potential as inward currents, are suppressed by all the employed blockers of ASICs.

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 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 asics gel s 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.

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 activation of ASICs [ 11 ] may be not just a coincidence.

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 asics gel kayano 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.

Considering our results and previously published data, we conclude that the effect of the ASIC blockers on GABAegic synaptic transmission is due to an at least partially postsynaptic but (predominantly) modulatory mechanism. Our results may be of importance for applied pharmacology, because ASICs are considered as therapeutic targets for neurological Изображение diseases and ASIC blockers as potential neuroprotectors [ 40 ].


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