In rat DRG neurons, pH 50 values ranging from 6.6 to et al.2006 ). The presence of ASIC2 in heteromeric ASICs tends to decrease the pH sensitivity of the channel (Table 3 ). Rat asics gel venture 6 mens DRG neurons express heteromeric ASICs of different compositions or homomeric ASIC1a or ASIC3. The proportion of these current subtypes varied between studies (Poirot et al.2006 ; Deval et al.2008 ). Rat DRG neurons express a high proportion of ASIC1 and ASIC3, with fewer asics gel torrance ASIC2a and 2b (Poirot et al.2006 ; Deval et al.2008 ; Boillat et al.2014 ). This is similar to the ASIC expression in humans (Delaunay et al.2012 ) but different from mouse DRGs that show a predominant expression of ASIC2a and 2b (Drew et al.2004 ; Hughes et al.2007 ).
Also, the synthetic molecule GMQ and related endogenous polyamines such as agmatine and arcaine (EC 50 e" 1 mM) have recently been shown to activate a sustained current in ASIC3 at physiological pHe (Yu et al.2010 asics gt 2000 6 womens ; Li et al.2011 ).In the following paragraph, we present the different pH sensors in PNS neurons, organized according to their pH sensitivity. Detailed information is provided in Table 3 . The varied expression pattern of ASICs and other pH sensitive ion channels suggests that pH changes may affect neuronal excitability to different extents in the various subpopulations of nociceptors (Figure 5 ).
Mild extracellular acidosis ( acidification to pH 7.2 6.4 ) inhibits different classes of K channels. Studies with human and rat DRG neurons provided evidence for an acidification induced depolarization that is mediated by K2P channels in this pH range (Baumann et al.2004 ; Cooper et al.2004 ). For several K2P channels, it was shown that their loss of function increased the sensation of pain (reviewed in Mathie and Veale, 2015 ). Acidification activates several types of ASICs in DRG neurons (Dirajlal et al.2003 ; Baumann et al.2004 ; Poirot et al.2006 ). In asics gt 2000 4 women's this pH range, the native ASIC currents are mediated by different ASIC heteromers containing ASIC1a and/or ASIC3 or by ASIC1a or ASIC3 homomers.
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
ENaC/ASIC channels (Kapoor et al.2011 ; Jeggle et al.2015 ).
