Operational Mechanism of the ‘Acid-sensing Ion Channel’ that Recognizes Internal Body Pain
team led by Professor Byung-Chang Suh identified the pain transmission
mechanism at the molecular level and presented new solutions for the
understanding of pain signals and the development of pain treatments.
Professor Byung-Chang Suh’s research team from the Department
of Brain and Cognitive Sciences succeeded in identifying a new operational
mechanism principle of the ‘Acid-sensing Ion Channel,’ which recognizes
internal pain in an organism.
The findings are expected to have a significant impact
on further studies focusing on the development of therapeutic agents that
control pain by providing a more precise understanding of the operational
mechanism of the ‘Acid-sensing Ion Channel’ that plays a pivotal role in
transmitting pain signals.
Pain is transmitted to the brain through nociceptive
nerves when pain spots that are distributed within an organism are stimulated.
Precisely, when pain causing substances are coupled to the plasma membrane of
the cells that constitute the pain spots, the pain signals are recognized.
Inside the organism, changes in pH levels occur under
pathophysiological conditions such as inflammation, ischemia, cancer, and the
like, which are accompanied by pain. The Acid-sensing Ion Channel (ASIC)
detects changes in pH levels in the organism and transmits the pain signal to
the brain. Biologically, many studies have been conducted regarding the Acid-sensing
Ion Channel; however, many areas are still unclear, especially in terms of the operational
mechanism and the cell membrane merging mechanism.
Professor Suh’s research team detected the cell
membrane merging mechanisms that modulate the activity of the Acid-sensing Ion
Channel at the molecular level, and it is this discovery and identification of
the new cell membrane merging mechanism of the Acid-sensing Ion Channel that had
remained unknown until now.
The research team identified through animal
experiments that there is a different cell membrane merging mechanism between
subunits of the Acid-sensing Ion Channel. ASIC2a can be merged to cell membranes
and has a cell membrane merging signal in protein, unlike ASIC2b, which cannot
be merged to cell membranes. In addition, ASIC2b has no cell membrane merging
signal and can only be merged to the cell membrane by forming a heteromeric
complex with ASIC2a.
The outcome of this study is meaningful since it
identified a new cell membrane merging mechanism of the Acid-sensing Ion
Channel, and furthermore is significant that it proposed a research direction
for a new understanding of the activity control mechanism of various ion
channels among subunits including ASIC2, ASIC2b and many other subunits.
Professor Byung-Chang Suh from
DGIST’s Department of Brain and Cognitive Sciences said, “Understanding of the
cell membrane merging and activity control mechanism of the Acid-sensing Ion
Channel plays an important role in identifying the pain signal transmission
system. That our study investigated a new control mechanism of the Acid-sensing
Ion Channel has important implications. Through continuous research, I’ll
strive to identify additional operations that act on the nervous system and
will develop new ways to treat pain.”
This research outcome was published in the online
edition of Scientific Reports, a
sister publication to the international academic journal Nature, on August 1, 2016. The study was conducted with the support
of junior executive researchers at the Ministry of Science, ICT, and Future
Planning; the Center for Nerve Aging and Regeneration Research at DGIST; and
the Center for Cerebral Cortex Research at the Korea Brain Research Institute.
Hae-Jin Kweon, Byung-Chang Suh, et.
al., “Acid-Sensing Ion Channel 2a (ASIC2a) Promotes Surface Trafficking of
ASIC2b via Heteromeric Assembly”, Scientific Reports 2016.