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J Neurophysiol (December 31, 2008). doi:10.1152/jn.90903.2008
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90903.2008v1
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Submitted on August 12, 2008
Revised on December 2, 2008
Accepted on December 22, 2008

The Na+/Ca2+ exchanger inhibitor, KB-R7943, blocks a nonselective cation channel implicated in chemosensory transduction

Adeline Pezier1*, Yuriy V Bobkov1, and Barry W. Ache1

1 University of Florida

* To whom correspondence should be addressed. E-mail: pezier{at}whitney.ufl.edu.

The mechanism(s) of olfactory transduction in invertebrates remains to be fully understood. In lobster olfactory receptor neurons (ORNs), a non-selective sodium-gated cation (SGC) channel, a presumptive transient receptor potential (TRP)-C channel homolog, plays a crucial role in olfactory transduction, at least in part by amplifying the primary transduction current. In order to better determine the functional role of the channel it is important to selectively block the channel independently of other elements of the transduction cascade, causing us to search for specific pharmacological blockers of the SGC channel. Given evidence that the Na+/Ca2+ exchange inhibitor, KB-R7943, blocks mammalian TRPC channels, we investigated this probe as a potential blocker of the lobster SGC channel. KB-R7943 reversibly blocked the SGC current in both inside- and outside-out patch recordings in a dose- and voltage-dependent manner. KB-R7943 decreased the channel open probability without changing single channel amplitude. KB-R7943 also reversibly and in a dose-dependent manner inhibited both the odorant-evoked discharge of lobster ORNs and the odorant-evoked whole-cell current. Our findings strongly imply that KB-R7943 potently blocks the lobster SGC channel and likely does so directly, not through its ability to block the Na+/Ca2+ exchanger.




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[Abstract] [Full Text] [PDF]




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