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Possible involvement of transient receptor potential ankyrin 1 in Ca 2+ signaling via T‐type Ca 2+ channel in mouse sensory neurons
Author(s) -
Nishizawa Yuki,
Takahashi Kenji,
Oguma Naoko,
Tominaga Makoto,
Ohta Toshio
Publication year - 2018
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.24208
Subject(s) - transient receptor potential channel , chemistry , trpv1 , agonist , biophysics , intracellular , t type calcium channel , capsaicin , voltage dependent calcium channel , sensory system , trpv , neuroscience , receptor , calcium , biochemistry , biology , organic chemistry
T‐type Ca 2+ channels and TRPA1 are expressed in sensory neurons and both are associated with pain transmission, but their functional interaction is unclear. Here we demonstrate that pharmacological evidence of the functional relation between T‐type Ca 2+ channels and TRPA1 in mouse sensory neurons. Low concentration of KCl at 15 mM (15K) evoked increases of intracellular Ca 2+ concentration ([Ca 2+ ] i ), which were suppressed by selective T‐type Ca 2+ channel blockers. RT‐PCR showed that mouse sensory neurons expressed all subtypes of T‐type Ca 2+ channel. The magnitude of 15K‐induced [Ca 2+ ] i increase was significantly larger in neurons sensitive to allylisothiocyanate (AITC, a TRPA1 agonist) than in those insensitive to it, and in TRPA1 −/− mouse sensory neurons. TRPA1 blockers diminished the [Ca 2+ ] i responses to 15K in neurons sensitive to AITC, but failed to inhibit 40 mM KCl‐induced [Ca 2+ ] i increases even in AITC‐sensitive neurons. TRPV1 blockers did not inhibit the 15K‐induced [Ca 2+ ] i increase regardless of the sensitivity to capsaicin. [Ca 2+ ] i responses to TRPA1 agonist were enhanced by co‐application with 15K. These pharmacological data suggest the possibility of functional interaction between T‐type Ca 2+ channels and TRPA1 in sensory neurons. Since TRPA1 channel is activated by intracellular Ca 2+ , we hypothesize that Ca 2+ entered via T‐type Ca 2+ channel activation may further stimulate TRPA1, resulting in an enhancement of nociceptive signaling. Thus, T‐type Ca 2+ channel may be a potential target for TRPA1‐related pain.