Pharmacological Properties of Cinnamaldehyde on NaChBac

Abstract

Recent breakthroughs in the structure determination of the bacterial voltage-gated sodium channel NavAb have revealed the full length Nav channel for the first time at atomic resolution. However, additional structures of Nav channels in different conformational states are still needed for further understanding of the conformational changes that take place in Nav channels during channel gating. Specifically, full-length structures of Nav channels in the resting state, open state, inactivated state, and drug-bound conformations are still missing. In our search for ligands that confine Nav channels in one of these conformational states we have turned our attention to cinnamaldehyde. We tested cinnamaldehyde, a compound that affects different subtypes of eukaryote Nav channels, on the bacterial Nav channel NaChBac expressed in Xenopus oocytes. Our results indicate that cinnamaldehyde has a dual effect on NaChBac: cinnamaldehyde not only decreases the peak current but also accelerates channel inactivation of this bacterial Nav channel in a concentration-dependent manner. Our recordings indicate that cinnamaldehyde stabilizes NaChBac in an inactivated state. This opens up perspectives to employ cinnamaldehyde as a molecular tool to aid crystallization of bacterial Nav channels in an inactivated conformation. We expect that such a structure could give important insight into the conformational changes that contribute to channel inactivation.