ÿþAlthough ASIC3 seems to predominate in the mediation of pain signals asics trainers from the periphery, ASIC1 or composite ASIC1/2 channels may have a more important role in pain sensation in the central nervous system (CNS). ASICs are expressed in the CNS in multiple locations including hippocampus, hypothalamus, midbrain, and cerebellum ( 6 , 215 , 274 , 307 ). While not all of these locations are involved in pain sensing, it is likely that ASICs identified in neurons of the dorsal horn are responsible for integrating peripheral pain signals before transmission to the cortex ( 32 ).

This held true for COS-7 cells exogenously expressing rat ASIC1a as well as for hippocampal neurons natively expressing rat ASICs ( 429 ). However, heteromeric channels formed of ASIC1 and ASIC2 are calcium impermeable. In rat models, global ischemia upregulated ASIC2 expression which would theoretically increase the population of heteromeric ASIC1/ASIC2 channels, acting to protect neurons from further ischemic attacks ( 210 ).Another asics running shoes mechanism of action was postulated for the role of ASICs in Huntington's disease, where mutations in the huntingtin gene lead to the accumulation of a mutant protein with an expanded polyglutamine tract and neuronal damage ( 34 ).

Still, this work is promising and suggests a role for ASICs in this disease and asics gel kayano possibly other CNS diseases where protein aggregation leads to neuronal death.Increased activity of ASICs has been implicated in both epilepsy and Parkinson's disease. Chemically induced seizures in rats are associated with a decrease in extracellular pH ( 351 ), likely due to efflux of lactic acid into the extracellular space. This raised the possibility that ASICs could be involved during seizure activity. Using pilocarpine to induce status epilepticus, Biagini et al. ( 45 ) found that the message level for ASIC2b was quickly (within 15 min), significantly, and persistently (sustained for at least 24 h) decreased in the hippocampus.

This could not be accounted for by asics gt 2000 simple neuronal death as treatment with diazepam and pentobarbital, which protect neurons, did not prevent the loss of ASIC message. ASIC1a expression was also reduced, but in a more restricted area. A more recent functional study has demonstrated that ASIC1 activity is, however, important in seizure termination, as seizures in ASIC1 knockout mice were much more severe than in their wild-type counterparts; similar results were obtained when ASIC1 was acutely inhibited in wild-type mice by intracranial injection of PcTx1 ( 443 ). Conversely, overexpression of ASIC1 shortened seizure duration.

Heteromeric ASIC1a/2b channels are more sensitive to reductions in pH than either ASIC1a or ASIC2b alone ( 174 ) and reducing extracellular pH (pH o ) to 6.8 was sufficient to decrease seizure activity in hippocampal slices ( 443 ). Loss of ASIC2b would therefore be predicted to decrease sensitivity of a heteromeric channel to changes in pH o . However, it is unknown whether heteromeric or homomeric channels are involved in seizure termination. Furthermore, seizure initiation and termination are highly complex processes, and the involvement of any channel type may differ based on the location of the seizure focus or even between species. Interestingly, expression of ASIC4 has been reported to be induced in pediatric patients with febrile seizures ( 338 ).

Overexpression of parkin suppressed ASIC2a currents asics netball trainers in a heterologous COS-7 cell system, while OAG (1-oleoyl-2-acetyl-sn-glycerol, a PKC activator)-stimulated currents in hippocampal neurons from a parkin knockout mouse were greatly potentiated ( 209 ). In contrast, OAG had no effect on ASIC currents recorded from wild-type mice. These data suggest that hyperactivity of ASIC contributes to neurodegeneration in Parkinson's disease.As with ENaCs, ASICs also have a role in sensory perception. ASICs are expressed in the retina, along with ENaCs ( 56 , 271 ). Retinal ganglion cells, which integrate signals from the retina also express amiloride-sensitive proton activated currents, consistent with ASIC expression ( 246 ).