In spite of the fact that the first evidence indicating reebok club c 85 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 reebok aztrek [ 17 ] and recent demonstration of functional crosstalk between ASICs and GABA A -receptors [ 10 , 11 ], the possible involvement of ASICs in the regulation of GABAergic transmission remained unclear. In our work we present evidence the reebok pump 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 found that GABAergic postsynaptic currents, recorded below their reversal potential as inward currents, are suppressed by all the employed blockers of ASICs.
Since suramin (500 ¼M) does not affect ASIC currents in hippocampal neurons [ 24 ] the above results also indicate that relative contribution of synaptic' ASIC current is much reebok pumps 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 ].
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 reebok classic leather lack of the apparent effect of 5b on inward PSCS in the presence of bicuculline, observed in our experiments.
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.