TY - JOUR
T1 - TRPA1-like channels enhance glycinergic transmission in medullary dorsal horn neurons
AU - Cho, Jin Hwa
AU - Jeong, Moon Young
AU - Choi, In Sun
AU - Lee, Heon Jin
AU - Jang, Il Sung
PY - 2012/8
Y1 - 2012/8
N2 - The effect of icilin, a potent agonist of transient receptor potential ankyrin 1 (TRPA1) and TRPM8, on glycinergic transmission was examined in mechanically isolated rat medullary dorsal horn neurons by use of the conventional whole-cell patch-clamp technique. Icilin increased the frequency of glycinergic spontaneous miniature inhibitory post-synaptic currents (mIPSCs) in a dose-dependent manner. Either allyl isothiocyanate(AITC) or cinnamaldehyde, other TRPA1 agonists, also increased mIPSC frequency, but the extent of facilitation induced by AITC or cinnamaldehyde was less than that induced by icilin. However, menthol, a TRPM8 agonist, had no facilitatory effect on glycinergic mIPSCs. The icilin-induced increase in mIPSC frequency was significantly inhibited by either HC030031, a selective TRPA1 antagonist, or ruthenium red, a non-selective transient receptor potential channel blocker. Icilin failed to increase glycinergic mIPSC frequency in the absence of extracellular Ca 2+, suggesting that the icilin-induced increase in mIPSC frequency is mediated by the Ca 2+ influx from the extracellular space. In contrast, icilin still increased mIPSC frequency either in the Na +-free external solution or in the presence of Cd 2+, a general voltage-dependent Ca 2+ channel blocker. The present results suggest that icilin acts on pre-synaptic TRPA1-like ion channels, which are permeable to Ca 2+, to enhance glycinergic transmission onto medullary dorsal horn neurons. The TRPA1-like channel-mediated enhancement of glycinergic transmission in medullary dorsal horn neurons would contribute to the regulation of pain information from the peripheral tissues. TRPA1 is predominantly expressed on sensory neurons, and activated by noxious cold and many chemical compounds including icilin. Our present results suggest that icilin acts on TRPA1-like channels, which are permeable to Ca 2+, to enhance glycinergic transmission onto medullary dorsal horn neurons. The TRPA1-like channel-mediated enhancement of glycinergic transmission in medullary dorsal horn neurons would contribute to the regulation of pain information from the peripheral tissues.
AB - The effect of icilin, a potent agonist of transient receptor potential ankyrin 1 (TRPA1) and TRPM8, on glycinergic transmission was examined in mechanically isolated rat medullary dorsal horn neurons by use of the conventional whole-cell patch-clamp technique. Icilin increased the frequency of glycinergic spontaneous miniature inhibitory post-synaptic currents (mIPSCs) in a dose-dependent manner. Either allyl isothiocyanate(AITC) or cinnamaldehyde, other TRPA1 agonists, also increased mIPSC frequency, but the extent of facilitation induced by AITC or cinnamaldehyde was less than that induced by icilin. However, menthol, a TRPM8 agonist, had no facilitatory effect on glycinergic mIPSCs. The icilin-induced increase in mIPSC frequency was significantly inhibited by either HC030031, a selective TRPA1 antagonist, or ruthenium red, a non-selective transient receptor potential channel blocker. Icilin failed to increase glycinergic mIPSC frequency in the absence of extracellular Ca 2+, suggesting that the icilin-induced increase in mIPSC frequency is mediated by the Ca 2+ influx from the extracellular space. In contrast, icilin still increased mIPSC frequency either in the Na +-free external solution or in the presence of Cd 2+, a general voltage-dependent Ca 2+ channel blocker. The present results suggest that icilin acts on pre-synaptic TRPA1-like ion channels, which are permeable to Ca 2+, to enhance glycinergic transmission onto medullary dorsal horn neurons. The TRPA1-like channel-mediated enhancement of glycinergic transmission in medullary dorsal horn neurons would contribute to the regulation of pain information from the peripheral tissues. TRPA1 is predominantly expressed on sensory neurons, and activated by noxious cold and many chemical compounds including icilin. Our present results suggest that icilin acts on TRPA1-like channels, which are permeable to Ca 2+, to enhance glycinergic transmission onto medullary dorsal horn neurons. The TRPA1-like channel-mediated enhancement of glycinergic transmission in medullary dorsal horn neurons would contribute to the regulation of pain information from the peripheral tissues.
KW - glycinergic mIPSCs
KW - icilin
KW - pre-synaptic facilitation
KW - trigeminal subnucleus caudalis
KW - TRPA1
UR - http://www.scopus.com/inward/record.url?scp=84864133403&partnerID=8YFLogxK
U2 - 10.1111/j.1471-4159.2012.07817.x
DO - 10.1111/j.1471-4159.2012.07817.x
M3 - Article
C2 - 22671314
AN - SCOPUS:84864133403
SN - 0022-3042
VL - 122
SP - 691
EP - 701
JO - Journal of Neurochemistry
JF - Journal of Neurochemistry
IS - 4
ER -