Patients with cardiac insufficiency receive drugs that affect the sodium pump in order to stabilize the heartbeat. Voltage-gated sodium channels. The family consists of at least 9 members and is largely responsible for action potential creation and propagation. The pore-forming alpha subunits are very large(up to 4,000 amino acids) and consist of four homologous repeat domains, comprising six transmembrane segments and transverse the cell membrane 24 times. They coassemble with a beta subunit that spans the membrane. Scorpion toxin has been used for classification of these channels.
Diagram of a voltage-sensitive sodium channel α-subunit. G – glycosylation, P – phosphorylation, S – ion selectivity, I – inactivation, positive (+) charges in S4 are important for transmembrane voltage sensing Frank H. Yu and William A. Catterall (2003) Overview of the voltage-gated sodium channel family in Genome Biol. 4(3): 207. ([http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrezamp.artid=153452 Full text online]).
Class Ia agents depress phase 0 depolarization and reduce Vmax which prolongs the action potential duration by slowing conductance, these agents include quinidine, procainamide, and disopyramide and should be used in conjunction with an AV node blocking agent such as digoxin or a beta-blocker. Class Ib agents have the fast onset and offset kinetics and little or no effect at slower heartbeats. These include lidocaine, mexiletine, tocainide, and phenytoin. Class Ic agents markedly depress the phase 0 depolarization. They are indicated for life-threatening ventricular tachycardia or ventricular fibrillation and for the treatment of atrial fibrillation. They are potentially pro-arrhythmic, especially in settings of structural heart disease, as in post-myocardial infarction and contraindicated in such instances.nbsp.