The structural determinants that distinguish tetrodotoxin sensitive and insensitive sodium channels.Chemical insights into how the heart rhythm drug flecainide targets the inner pocket of the ion channel and plugs the central pore that conducts sodium ions.Still other mutations, found in Brugada syndrome, can impair or block the conductance of sodium ions. Others cause altered function by creating a channel protein hole that leaks sodium continuously. Some mutations interfere with the activation or inactivation of the sodium channel. There are many parts of the sodium channel protein that can be disrupted by mutations. Structural insights into the mode of action of various arrhythmia mutations.A description of some of the characteristics of the NaV1.5 channel that distinguish it from other sodium ion channels found in heart cells, as well as in nerve and muscle cells.They wanted to explore important structural features of these sodium channels and relate their configuration to their actions in normal physiological function, dysfunction, disease mutations, toxin sensitivity and the pharmacology of antiarrhythmic drugs.Īccording to the scientists, their experiments provide a blueprint for understanding many various aspects of cardiac sodium channels.Īmong the key findings from this work were: To obtain a high-resolution, 3-D map of the channels, the scientists used advanced cryo-electron microscopy at the new Beckman Center for Cryo-EM at the UW. In their recent study, the researchers sought to learn, among other things, how drugs like flecainide act within the predominant form of sodium channels found in cardiac cells. This condition can often be treated effectively with the drug flecainide. For example, as UW Medicine physician Michael Lenaeus, a UW assistant professor of medicine, Division of General Internal Medicine, and a co-author of the study, noted, atrial fibrillation, or 'A-fib,' is increasingly prevalent among older Americans. Sodium ions - a type of charged particles - pass through these protein passageways in the membrane boundary between the outside and inside of the cell.įortunately, many heart rhythm disturbances can be treated with drugs that block cardiac sodium channels. The rate at which the impulse is propagated through the heart tissue relies on actions taking place at the molecular level in tiny protein pores present in cardiac cell membranes. For each heartbeat, electrical waves travel across a healthy heart in a pattern that controls its filling and pumping in a tightly coordinated manner. The heart is both a plumbing and electrical marvel. 'The cardiac sodium channel not only initiates the heartbeat, mutations in it also cause deadly arrhythmias, and antiarrhythmic drugs act directly on it to control cardiac rhythms,' explained Catterall. The first authors are Daohau Jiang and Hui Shi, UW postdoctoral fellows in pharmacology. 19 in Cell in the paper, 'Structure of the Cardiac Sodium Channel.' The senior authors are William Catterall and Ning Zheng, both UW School of Medicine professors of pharmacology. This structural information could become the basis for developing better diagnostics and drugs for life-threatening heart rhythm problems, according to the researchers from the University of Washington School of Medicine working in this area.

Atomic heart map