The finding that asics trainers PcTx1 and ASIC1 antisense oligo-deoxynucleotides infused into the intrathecal space both had analgesic effects further suggests a role for ASIC1 in the central mediation of pain ( 108 , 272 ). Moreover, recently defined interactions between ASICs and peptides found within the CNS, such as the dynorphins, reinforce the possibility that CNS ASICs may be manipulated to manage pain ( 347 , 426 ).

In general, and despite data from knockout animals, a reasonable case can be made for ASICs, particularly ASIC3, being attractive targets for novel analgesic strategies. Acid-induced pain in humans was attenuated by treatment with amiloride ( 392 ), suggesting that inhibitors of ASICs, potentially including peptide toxins and aminoglycoside antibiotics ( 145 ), in addition to the more conventional amiloride and NSAID asics running shoes analogs ( 128 ), could play a role in the treatment of pain, while avoiding the behavioral issues associated with opiates ( 272 ). A more detailed account of the literature surrounding the role of ASICs in pain is provided in an asics gel kayano excellent recent review ( 98 ).

Studies of ASIC1 in mice have implicated it in synaptic plasticity, learning, and memory formation (409 411). In the CNS, the protein appears to localize with the postsynaptic density-95 protein (PSD-95), which likely targets ASIC1 to areas of high synaptic density ( 409 , 410 ). Behavioral tests of mice overexpressing ASIC1 found increased acquired fear related behavior ( 411 ), while ASIC1 knockout mice showed a deficit in cued and contextual fear conditioning ( 409 ), suggesting that perhaps asics gt 2000 ASIC1 could play a role in anxiety or fear learning. Interestingly, it has recently been reported that decreased brain pH resulting from hypercarbia also elicits fear in mice, a behavioral response that is attenuated by ASIC1 knockout ( 442 ).

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 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 ).

Touch sensation also involves ASICs, although the exact role of the different channels asics netball trainers is still somewhat unclear. Pacinian corpuscles express ASIC1 and 2 in humans ( 62 ), although loss of ASIC1 expression did not appear to affect touch sensation in mice ( 294 ). In contrast, ASIC3 has been suggested to be the important mediator of touch sensation in mice ( 315 ).One of the major pathologies for which a potential role of ASICs and ENaCs is currently emerging is cancer. Multiple studies have shown that ASICs and ENaCs are associated with cell migration and proliferation, even in nontumor cells ( 48 , 83 , 97 , 155 , 156 ).