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[Functional analysis of acid sensing ion channels]
Shoichi Shimada1, Hisao Yamamura, Takashi Ueda
1Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, 467-8601 Japan.
Nihon Shinkei Seishin Yakurigaku Zasshi = Japanese Journal of Psychopharmacology
|October 16, 2004
Summary
Acid-sensing ion channels (ASICs) like ASIC2a and ASIC2b are involved in taste and pain. ASICs are key acid sensors in human pain, while TRPV1 plays a role in extreme acidity.
Area of Science:
- Neuroscience
- Molecular Biology
- Sensory Physiology
Background:
- Acid-sensing ion channels (ASICs) are proton-gated channels involved in various physiological processes.
- ASIC2a is implicated in sour taste detection in rats.
- ASICs also contribute to acid-induced pain (nociception) in mammals.
Purpose of the Study:
- To investigate the role of ASIC2b in rat taste cells and its interaction with ASIC2a.
- To elucidate the contribution of ASICs and TRPV1 to acid-induced pain in humans.
Main Methods:
- Transcript analysis and immunohistochemistry in rat taste papillae.
- Coimmunoprecipitation to study protein interactions.
- Oocyte electrophysiology to characterize channel function.
- Human psychophysical experiments involving acid infusion and drug blockers (amiloride, capsazepine).
Main Results:
- ASIC2b transcripts and proteins are expressed in rat taste papillae, co-localizing with ASIC2a in some taste cells.
- ASIC2a and ASIC2b associate to form functional channels with amiloride-insensitive currents.
- Acid-induced pain in human skin is primarily blocked by amiloride, suggesting ASIC involvement.
- Capsazepine (TRPV1 inhibitor) shows partial blocking effect only under severe acidification (pH 5.0).
Conclusions:
- ASIC2a and ASIC2b form functional channels in rat taste cells, explaining amiloride-insensitive sour taste responses.
- ASICs (ASIC1a and ASIC3) are the primary sensors for acid-induced pain in human nociceptors.
- TRPV1 contributes to acid-induced nociception mainly under extreme acidic conditions.