Osmomechanical-Sensitive TRPV Channels in Mammals

Within the transient receptor potential (TRP) superfamily of ion channels (Cosens and Manning, 1969; Montell and Rubin, 1989; Wong et al., 1989; Hardie and Minke, 1992; Zhu et al., 1995), the TRPV subfamily stepped into the limelight in 1997 (Colbert et al., 1997; Caterina et al., 1997), when its founding members, OSM-9 in Caenorhabditis elegans and TRPV1 in mammals, were first reported. OSM-9 was identified through genetic screening for worms’ defects in osmotic avoidance (Colbert et al., 1997). TRPV1 was identified by an expression cloning strategy (Caterina et al., 1997). (This is also true for TRPV5 and TRPV6, which will not be discussed in this chapter because, up to now, they have not been implicated in osmotic and mechanical signaling.) TRPV2, TRPV3, and TRPV4 were identified by a candidate gene approach, respectively (Caterina and Julius, 1999; Peier et al., 2002; Gunthorpe et al., 2002; Xu et al., 2002; Kanzaki et al., 1999; Liedtke et al., 2000; Strotmann et al., 2000; Wissenbach et al., 2000). The latter strategy also led to the identification of four additional C. elegans ocr genes (Tobin et al., 2002) and two Drosophila trpv genes, Nanchung (NAN) and Inactive (IAV) (Kim et al., 2003; Gong et al., 2004). The TRPV channels can be subgrouped into four branches by sequence comparison. One branch includes four members of mammalian TRPVs, TRPV1, TRPV2, TRPV3, and TRPV4; in vitro whole cell recording showed that they respond to temperatures higher than 42°C, 52°C, 31°C, and 27°C, respectively, suggesting that they are involved in thermosensation, hence the term thermo-TRPs. Illuminating review articles on thermo-TRPs are available for in-depth reading (Clapham, 2003; Patapoutian, 2005; Tominaga and Caterina, 2004; Caterina and Julius, 1999; Caterina and Montell, 2005). The second mammalian branch includes the Ca2+-selective channels, TRPV5 and TRPV6, possibly subserving Ca2+ uptake in the kidney and intestine (Hoenderop et al., 1999; den Dekker et al., 2003; Peng et al., 1999, 2003). One invertebrate branch includes C. elegans OSM-9 and Drosophila IAV; the other branch comprises OCR-1 to OCR-4 in C. elegans and Drosophila NAN.This chapter elucidates the role of mammalian TRPV channels in signal transduction in response to osmotic and mechanical stimuli, as well as provides comments on selected recent insights regarding other TRP ion channels that respond to osmotic and mechanical cues. These “osmo- and mechano-TRPs” (Liedtke and Kim, 2005) are TRPV1 (Sharif-Naeini et al., 2006; Zaelzer et al., 2015), TRPV2 (Muraki et al., 2003), TRPV4 (Liedtke et al., 2000; Strotmann et al., 2000), TRPC1 (Chen and Barritt, 2003), TRPC3 (Quick et al., 2012), TRPC6 (Spassova et al., 2006), TRPA1 (Corey et al., 2004; Nagata et al., 2005), TRPP2 (Nauli et al., 2003), TRPP3 (Murakami et al., 2005), TRPM3 (Grimm et al., 2003), TRPM4 (Earley et al., 2004), TRPM7 (Numata et al., 2007), and TPML3 (Di Palma et al., 2002). A full listing of mammalian TRPs involved in osmomechanosensation can be found in Table 5.1.