The use of toxins showed that ASIC1 [url=http://www.krios-hyperion.com/asics-c-1/asics-fuzex-rush-c-1_8/]asics fuzex rush[/url] channels of the PNS are also involved in pain sensation. Injection of the ASIC activating MIT toxin of the Texas coral snake in the mouse paw induced pain that depended on the presence of ASIC1a (Bohlen et al.2011 ). Peripheral injection of Mambalgin, which inhibits several ASIC subtypes, exerted an analgesic action due to its inhibition of ASIC1b (Diochot et al.2012 ). ASICs are also expressed in pain processing areas of the CNS. Administration of PcTx1 or Mambalgin to the CNS inhibited pain behaviours, indicating a role of central ASICs in pain sensation (Mazzuca et al.2007 ; Diochot et al.2012 ), in addition to the more obvious role of ASICs as pH sensors in the PNS.
Two mouse models in which ASIC currents were suppressed expression of a dominant negative ASIC3 mutant and a triple ASIC1a/ASIC2/ASIC3 knockout showed increased pain behaviour, indicating that [url=http://www.krios-hyperion.com/asics-c-1/asics-gel-lyte-v-mens-c-1_9/]asics gel lyte v mens[/url] some aspects of the role of ASICs in pain sensation are not yet understood (Mogil et al.2005 ; Kang et al.2012 ).The neuropeptides CGRP and substance P contribute to inflammation and are secreted from sensory nerve terminals in response to tissue acidification. CGRP induces vasodilatation and substance P promotes increased vascular [url=http://www.krios-hyperion.com/asics-c-1/asics-gel-lyte-womens-c-1_10/]asics gel lyte womens[/url] permeability leading to plasma extravasation during neurogenic inflammation (Walker et al.2010 ; Hoyer and Bartfai, 2012 ).
Because the neuropeptide secretion is Ca 2 dependent, TRPV1 and ASICs, which induce Ca 2 entry directly or via depolarization induced activation of Ca v s, may mediate acidification induced neuropeptide secretion. Experiments using specific pharmacological inhibitors or gene knockout identified TRPV1 but not ASICs as the pH sensors for the acid induced neuropeptide secretion from sensory neurons (Fischer et al.2003 ; Pan et al.2010 ; Weller et al.2011 ; Boillat et al.2014 ). It is likely that the transient ASIC current is too short [url=http://www.krios-hyperion.com/asics-c-1/asics-gel-nimbus-20-mens-c-1_11/]asics gel nimbus 20 mens[/url] to induce neuropeptide release and that a sustained current, as the one mediated by TRPV1, is required.
Expression of the different ASIC subunits has been shown in primary afferent neurons innervating the skin, eye, ear, taste buds, heart, gut, skeletal muscle and joints (reviewed in Wemmie et al.2013 ; Kellenberger and Schild, 2015 ). ASIC function has been measured in small and large diameter neurons of the trigeminal, nodose and dorsal root ganglia of mice and rats (Benson et al.2002 ; Poirot et al.2006 ; Boillat et al.2014 ; Deval and Lingueglia, 2015 ). ASIC like currents have also been measured from human dorsal root ganglion (DRG) neurons (Baumann et al.2004 ). Sensory neurons express homo and heterotrimeric ASICs, producing current subtypes with different pH dependence.
Because ASIC currents are mostly transient due to rapid desensitization, they last only a few seconds, even if an acidic extracellular environment persists. In addition, at a pH slightly below the physiological 7.4, some ASIC subtypes desensitize without apparently opening and are not available for subsequent activation in the case of further acidification. From these observed properties, it is expected that ASICs are best adapted to sense rapid changes in pH, but will not report a persistent changed pH. If [url=http://www.krios-hyperion.com/asics-c-1/asics-gel-nimbus-20-review-c-1_12/]asics gel nimbus 20 review[/url] a pH change occurs slowly, as is the case in ischaemia and inflammation, it may even desensitize ASICs rather than activating them.
ENaC ² and ³ subunits are also expressed in vascular smooth muscle cells where they contribute to pressure induced constriction. Similarly, ASICs in vascular smooth muscle cells probably regulate vascular tone and chemotactic migration (Drummond et al.2008 ). Other overlapping functions of ENaC and ASICs may still be discovered. Interestingly, two recent studies indicate that overexpression of ASICs together with ENaC may lead to the formation of hybrid [url=http://www.krios-hyperion.com/asics-fuzex-rush-p-140.html][img]http://www.krios-hyperion.com/images/shoes/asics fuzex rush-698fra.jpg[/img][/url] ENaC/ASIC channels (Kapoor et al.2011 ; Jeggle et al.2015 ).
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