Journal
NEUROSCIENCE
Volume 154, Issue 4, Pages 1467-1476Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neuroscience.2008.04.048
Keywords
mustard oil; TRP ion channel; calcium; polyphosphate; trigeminal neuron; pungent chemicals
Categories
Ask authors/readers for more resources
Our recent study has shown that activation of transient receptor potential All channel (TRPA1) by pungent chemicals such as allyl-isothlocyanate (AITC) requires an unidentified cytosolic factor whose action can be mimicked by inorganic polyphosphates. Thus, AITC and other pungent chemicals fail to activate TRPA1 in excised patches. It is unclear whether TRPA1 switches to a conformation that is insensitive to the pungent chemicals, or whether TRPA1 simply becomes completely non-functional and insensitive to all activators when the cytosolic factor is absent. To help distinguish between these possibilities, the effects of Delta(9)-tetrahydrocannabinol (THC) and Ca2+ that are structurally different from pungent chemicals were tested on AITC-sensitive and AITC-insensitive states of TRPA1. In HeLa cells transiently expressing mouse TRPA1, activation of TRPA1 by THC was slow and weak from the extracellular side (cell-attached; K-1/2 >20 mu M), but was faster and more potent from the intracellular side (inside-out; K-1/2, similar to 0.7 mu M), and this did not require the presence of a polyphosphate. Similar results were observed in rat trigeminal neurons. Increasing the extracellular [Ca2+] from similar to 0-1-3 mM activated TRPA1 in cell-attached patches. Elevation of cytosolic [Ca2+] using thapsigargin (inhibitor of Ca2+-ATPAse) and histamine (that elevates IP3) also activated TRPA1 in cell-attached patches. Similar to pungent chemicals, Ca2+ (1-5 mu M) failed to activate TRPA1 in inside-out patches, unless polyphosphates were present. These results show that TRPA1 can exist in different functional states: a native state (cell-attached patch) and a non-native state (excised patch). THC can activate TRPA1 even in the absence of polyphosphates, whereas pungent chemicals and Ca2+ require it for activation. (C) 2008 IBRO. Published by Elsevier Ltd. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available