In spite of the fact reebok look that the first evidence indicating 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 the same cells the suppression of postsynaptic currents, recorded above their reebok classic reversal potential as outward currents was statistically insignificant.Apart from the chemical dissimilarity of amiloride and diminazene, they are structurally different [ 24 ], and mechanisms of their action on ASICs are different as well [ 24 ]. reebok shoes Similarly, amiloride and 5b have different mechanisms of action on ASICs [ 21 ]. Indeed, 5b is an orthosteric antagonist of ASIC1 [ 21 ] while amiloride is an open channel blocker [ 33 ].

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 the pump 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.

Lack of substantial direct involvement of ASICs in PSCs generation in our experiments can be also supported by comparing the possible relative contribution of ASIC current to total synaptic current. Based on the results of our experiments with application of bicuculline alone, the relative contribution of ASIC currents to total synaptic current is less than 9 % reebok pump (8.29 ± 2.24). Our experiments using 5b and suramin suggest an even lower percentage. Indeed, the residual currents were nearly unaffected in presence of 5b (1 ¼M) but strongly suppressed (to 16.9 ± 4.3 % of control) by suramin at 200 ¼M concentration.

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 diseases and ASIC blockers as potential neuroprotectors [ 40 ].