Degenerin/ENaC channels

Deg/ENaC channels serve diverse functions in physiology. In some invertebrate animals as typied by the nematode C. elegans, some members of the Deg/ENaC channel family function as ionotropic molecular sensory transducers in peripheral sensory neurons involved in perception of the external environment Contents 26.1 Introduction 395 26.2 Expression and function of Deg/ENaC channels 395 26.2.1 Physiological role of Deg/ENaC proteins 396 26.2.2 FaNaC: A peptide-gated Na⁺ channel 397 26.2.3 HyNaC: e ancestral Deg/ENaC channel 398 26.2.4 Deg: Mechanosensitive channels of the nematode 398 26.2.5 Ppk: Deg/ENaC channels of insects 399 26.2.6 ASIC: Acid-sensing Na⁺ channels expressed in mammalian neurons 400 26.2.7 ENaC: e mammalian epithelial Na⁺ channel involved in transport 401 26.2.8 BLINaC: e mammalian Deg/ENaC channel expressed in both neurons and epithelial cells 402 26.3 Evolution of Deg/ENaC channels 403 26.3.1 Emergence of ASIC 403 26.3.2 Emergence of ENaC 404 26.4 Structure of Deg/ENaC channels 404 26.4.1 Pore of Deg/ENaC channels 405 26.4.2 Gate of Deg/ENaC channels 406 26.5 Deg/ENaC channels in human diseases 406 26.5.1 Role of ASIC in pathology 406 26.5.2 Regulation of ENaC by intracellular signaling 407 26.5.3 Pathology arising from ENaC dysfunction 407 References 408 (Bianchi and Driscoll, 2002; Mano and Driscoll, 1999). In others, as typied by Helix aspersa, Deg/ENaC channels function as neuropeptide-gated channels in central neurons controlling excitation and synaptic transmission (Cottrell, 1997). In contrast, ENaC, which is expressed in epithelia of terrestrial vertebrates, functions during ion transport and consequently is involved in homeostatic control of uid volumes and electrolyte content, making this channel a key end eector in the regulation of blood pressure (Garty and Palmer, 1997; Kellenberger and Schild, 2002). Mammalian ASIC, which are expressed in both peripheral and central neurons, more closely parallel the function of invertebrate Deg/ENaC channels as sensory receptors and during neurotransmission in the postsynaptic cell (Bianchi and Driscoll, 2002; Sherwood et al., 2012). Seven Deg/ENaC homologs, the invertebrate FaNaC, HyNaC, Deg and Ppk, and the mammalian ENaC, ASIC, and BLINaC are discussed here as proteins representative of the family and these various functions.