Modeling of benzocaine analog interactions with the D4S6 segment of NaV4.1 voltage-gated sodium channels.

Local anesthetics (LAs) are compounds that inhibit the propagation of action potentials in excitable tissues by blocking voltage-gated Na+ channels. Mutagenesis studies have demonstrated that several amino acid residues are important sites of LA interaction with the channel, but these studies provide little information regarding the molecular forces that govern drug-binding interactions, including the binding orientation of drugs. We used computational methods to construct a simple model of benzocaine analog binding with the D4S6 segment of rat skeletal muscle (NaV4.

Cardiotoxic and antiarrhythmic tertiary amine local anesthetics: sodium channel affinity vs. sodium channel gating.

Tertiary amine local anesthetics (LAs) are clinically valuable agents for controlling pain and for treating some cardiac arrhythmias. These drugs inhibit conduction of electrical activity by blocking voltage-gated sodium channels. Interestingly, LAs can influence the conduction of electrical activity in heart muscle without markedly altering normal skeletal muscle activity.

Voltage-dependent inhibition of rat skeletal muscle sodium channels by aminoglycoside antibiotics.

Aminoglycoside (AG) antibiotics interact with numerous biological molecules, including some voltage-gated ion channels. The present study demonstrates that 4,5-disubstituted (neomycin class) and 4,6-disubstituted (kanamycin class) AGs inhibit whole-cell currents through cloned rat skeletal muscle sodium channels (mu1, Na(V)4.1).

Comparison of aconitine-modified human heart (hH1) and rat skeletal (mu1) muscle Na+ channels: an important role for external Na+ ions.

Neurotoxins such as aconitine (AC) bind to receptor site 2 on voltage-gated sodium channels and modify channel kinetics. Although AC modification typically induces hyperpolarizing shifts in sodium channel activation, the effects on channel inactivation seem to vary depending on the tissue origin of the channel. In the present study, the alpha subunits of human heart (hH1) and rat skeletal muscle (mu1) sodium channels were transiently expressed in human embryonic kidney (HEK293t) cells.