[Abstract Title]. - Society for Neuroscience

Abstract: TRPM7 channels are Ca 2+ -permeable non-selective cation channels whose activation
has been shown to be involved in ischemic neuronal cell death. In addition to Ca 2+ , previous
studies have suggested that these channels might be zinc permeable. Here we show further
evidence that activation of TRPM7 channels induces zinc accumulation, and that zinc entry
through these channels plays an important role in cell injury. First, fluorescent imaging with
FluoZin3 demonstrated higher intracellular zinc concentration in HEK293 cells over-expressing
TRPM7. Second, over-expression of TRPM7 channels increased susceptibility of these cells to
zinc-induced injury. Third, in cultured mouse cortical neurons, removal of Ca 2+ /Mg 2+ from
extracellular solution, a condition known to facilitate the opening of TRPM7 channels, also
augmented zinc-induced cell death and the degree of cell injury was correlated with the
increment of intracellular zinc. Fourth, this zinc toxicity in neurons was attenuated by
nonspecific TRPM7 blockers Gd 3+ and 2-APB. Taken together, these results suggest that
activation of TRPM7 channels is associated with zinc-dependent toxicity.
Disclosures: K. Inoue, None; Z. Xiong, None.
Poster
235. Ion Channels in Disease I
Time: Sunday, November 16, 2008, 1:00 pm - 5:00 pm
Program#/Poster#: 235.11/C57
Topic: B.04.d. Ion channels and disease
Title: TRPA1 is a potential target for the treatment of asthma
Authors: M. M. MORAN 1 , D. DEL CAMINO 2 , J. STRICKER 3 , J. WITEK 4 , J. A. CHONG 5 ,
*N. J. HAYWARD 6 ;
1 Director of Biol., 2 Project Leader, 3 Dept. of Pharmacol., 4 Director of Cell Biol., 5 Director of
Target Discovery, 6 VP: Pharmacol. & Toxicology, Hydra Biosci., Cambridge, MA
Abstract: TRPA1 is a member of the Transient Receptor Potential superfamily of calciumpermeable,
non-selective cation channels. It is selectively expressed in neurons of the dorsal root,
trigeminal and nodose ganglia. Recent work has shown that TRPA1 responds to a number of
environmental irritants known to cause respiratory distress, including formaldehyde, acrolein and
oxidants. Here we probed the role of TRPA1 in an ovalbumin-induced model of asthma using a
selective TRPA1 antagonist we identified. We show that blocking TRPA1 not only decreases
airway hyperresponsiveness, but also decreases infiltration of the lung by a range of immune
cells. This work implicates TRPA1 as a possible target for the treatment of asthma and other
pulmonary diseases. In addition, these data suggest that neurogenic inflammation plays a critical
role in the development of pathology in the OVA-model.