Inhibition of the Human Neuronal Sodium Channel Na1.9 by Arachidonyl-2-Chloroethylamide, An Analogue of Anandamide in a hNa1.9/rNa1.4 Chimera, An Experimental and in Silico Study.

Cannabinoids regulate analgesia, which has aroused much interest in identifying new pharmacological therapies in the management of refractory pain. Voltage-gated Na+ channels (Nas) play an important role in inflammatory and neuropathic pain. In particular, Na1.

Mefloquine inhibits voltage dependent Na1.4 channel by overlapping the local anaesthetic binding site.

Mefloquine constitutes a multitarget antimalaric that inhibits cation currents. However, the effect and the binding site of this compound on Na channels is unknown. To address the mechanism of action of mefloquine, we employed two-electrode voltage clamp recordings on Xenopus laevis oocytes, site-directed mutagenesis of the rat Na channel, and a combined in silico approach using Molecular Dynamics and docking protocols.

Characterization of specific allosteric effects of the Na channel β1 subunit on the Na1.4 isoform.

The mechanism of inactivation of mammalian voltage-gated Na channels involves transient interactions between intracellular domains resulting in direct pore occlusion by the IFM motif and concomitant extracellular interactions with the β1 subunit. Naβ1 subunits constitute single-pass transmembrane proteins that form protein-protein associations with pore-forming α subunits to allosterically modulate the Na influx into the cell during the action potential of every excitable cell in vertebrates. Here, we explored the role of the intracellular IFM motif of rNa1.

Identification of Navβ1 residues involved in the modulation of the sodium channel Nav1.4.

Voltage-gated sodium channels (VGSCs) are heteromeric protein complexes that initiate action potentials in excitable cells. The voltage-gated sodium channel accessory subunit, Navβ1, allosterically modulates the α subunit pore structure upon binding. To date, the molecular determinants of the interface remain unknown.

A residue W756 in the P-loop segment of the sodium channel is critical for primaquine binding.

Our study on the wild-type and mutants of the voltage-dependent sodium channel in the rat skeletal muscle Na(v) 1.4 was to examine the possible binding site of primaquine PQ by using an experimental approach. We used a standard voltage-clamp in oocytes.

The increase in zinc levels and upregulation of zinc transporters are mediated by nitric oxide in the cerebral cortex after transient ischemia in the rat.

The transient occlusion of cerebral arteries causes an increase in zinc levels in the brain, which is associated with a production of nitric oxide (NO). The types of zinc transporters (ZnT) involved in zinc homeostasis in the cerebral cortex after hypoxia-ischemia are not completely known. We studied the effect of the transient occlusion (10 min) of the common carotid artery (CCA) on NO-induced zinc levels, ZnT mRNA expression, and cell-death markers in the cerebral cortex-hippocampus of the rat.