*3.3. ASIC Channels*

Acid-sensing ion channels (ASICs) were initially implicated in mechanotransduction because their phylogenetic homologs in *Caenorhabditis elegans*—the mechanosensory (MEC) channel subunits—are essential for the perception of touch. Three members of the ASIC family (ASIC1-3) are expressed in peripheral mechanoreceptors and nociceptors in mammals. Six ASIC proteins encoded by four genes have been identified, ASIC1a, ASIC1b, ASIC2a, ASIC2b, ASIC3, and ASIC4, which differ in their kinetics, external pH sensitivity, tissue distribution, and pharmacological properties [122]. ASIC-2 mRNA is expressed in both small-diameter and large-diameter neurons and colocalized within single sensory neurons in the TG [123]. One-third of TG neurons that project towards the tooth pulp are immunoreactive (IR) to ASIC3 [124]. A single-cell RT-PCR study revealed that the ASIC3 mRNA is expressed in 67% of pulpal afferent neurons [58,59]. Human odontoblasts display immunoreactivity for ASIC2 as well as the ENaC-β and ENaC-γ, but not the ENaC-α, subunits [125]. These findings suggest a role for ASIC3 in the mechanotransduction of tooth sensitivity.
