The Na /Ca Exchanger Inhibitor, KB-R7943, Blocks a Nonselective Cation Channel Implicated in Chemosensory Transduction

Pezier A, Bobkov YV, Ache BW. The Na /Ca exchanger inhibitor, KB-R7943, blocks a nonselective cation channel implicated in chemosensory transduction. J Neurophysiol 101: 1151–1159, 2009. First published December 31, 2008; doi:10.1152/jn.90903.2008. The mechanism(s) of olfactory transduction in invertebrates remains to be fully understood. In lobster olfactory receptor neurons (ORNs), a nonselective 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. 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 /Ca exchange inhibitor, KB-R7943, blocks mammalian TRPC channels, we studied this probe as a potential blocker of the lobster SGC channel. KB-R7943 reversibly blocked the SGC current in both insideand outside-out patch recordings in a doseand 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 odorantevoked whole cell current. Our findings strongly imply that KBR7943 potently blocks the lobster SGC channel and likely does so directly and not through its ability to block the Na /Ca exchanger.