A sensory neuron-specific, proton-gated ion channel

Abstract

Proton-gated channels expressed by sensory neurons are of particular interest because low pH causes pain. Two proton-gated channels, acid-sensing ionic channel (ASIC) and dorsal root ASIC (DRASIC), that are members of the amiloride-sensitive ENaC͞Degenerin family are known to be expressed by sensory neurons. Here, we describe the cloning and characterization of an ASIC splice variant, ASIC-␤, which contains a unique N-terminal 172 aa, as well as unique 5 and 3 untranslated sequences. ASIC-␤, unlike ASIC and DRASIC, is found only in a subset of small and large diameter sensory neurons and is absent from sympathetic neurons or the central nervous system. The patterns of expression of ASIC and ASIC-␤ transcripts in rat dorsal root ganglion neurons are distinct. When expressed in COS-7 cells, ASIC-␤ forms a functional channel with electrophysiological properties distinct from ASIC and DRASIC. The pH dependency and sensitivity to amiloride of ASIC-␤ is similar to that described for ASIC, but unlike ASIC, the channel is not permeable to calcium, nor are ASIC-␤-mediated currents inhibited by extracellular calcium. The unique distribution of ASIC-␤ suggests that it may play a specialized role in sensory neuron function.

The acid-sensing ion channel 2 (ASIC2) of ciliated cells in the developing rat nasal septum

“…For the nervous systems, differences in the localization of ASIC subtypes have been reported: all ASIC subtypes were observed in the peripheral nervous system (PNS) while ASIC1a, 2a and 2b were found in the spinal cord and ASIC1a, 2a and 4 in the brain (Price et al, 1996;Chen et al, 1998;Babinski et al, 2000;Peng et al, 2004;Lingueglia, 2007). We also reported that ASIC2 expression was detected in the ciliated cells of the rat trachea although the subtypes were not clarified in our previous study (Kikuchi et al, 2008).…”

“…Among them, ASIC1 and ASIC2 have spliced variants. The ASIC1 gene spliced variants are ASIC1a and ASIC1b, and ASIC2 spliced variants are ASIC2a and ASIC2b (Lingueglia et al, 1997;Waldmann et al, 1997;Chen et al, 1998;Bassler et al, 2001). No spliced variants of ASIC3 or ASIC4 have been detected.…”

Acid-sensing ion channels (ASICs) as pharmacological targets for neurodegenerative diseases

“…In addition to conducting Na + ions, homomeric ASIC1a channels are permeable to Ca 2+ ions [10,12,13]. ASIC1b (ASIC1β) is a splice variant of ASIC1a with restricted expression in sensory neurons [24]. Homomeric ASIC1b channels respond to pH o drop with a similar transient current and a pH 0.5 of ∼5.9 [24,25].…”

“…ASIC1b (ASIC1β) is a splice variant of ASIC1a with restricted expression in sensory neurons [24]. Homomeric ASIC1b channels respond to pH o drop with a similar transient current and a pH 0.5 of ∼5.9 [24,25]. Unlike ASIC1a, homomeric ASIC1b channels do not show Ca 2+ permeability.…”

“…It reversibly inhibits the ASIC currents with an IC 50 of 10 -50 μM [10,13,24,28,42]. Similar to its effect on the ASIC currents, amiloride inhibits acidinduced increase of [Ca 2+ ] i and membrane depolarization [10,12,43,44].…”