Myocardial action potential and action of antiarrhythmic drugs
- Jonathan C Makielski, MD, FACC
Jonathan C Makielski, MD, FACC
- Professor of Medicine
- University of Wisconsin-Madison
Cardiac excitability refers to the ease with which cardiac cells undergo a series of events characterized by:
- Sequential depolarization and repolarization
- Communication with adjacent cells
- Propagation of the electrical activity in a normal or abnormal manner
The heartbeat arises from organized flow of ionic currents through ion-specific channels in the cell membrane, through the myoplasm and gap junctions that connect cells, and through the extracellular space (figure 1) [1,2]. Mutations in genes encoding the subunits and associated proteins of these channels have been associated with familial arrhythmic syndromes and sudden cardiac death. Examples include the congenital long QT syndrome (sodium and potassium current), the Brugada syndrome (mainly sodium current), and congenital heart block (sodium current). (See "Genetics of congenital and acquired long QT syndrome" and "Brugada syndrome: Epidemiology and pathogenesis" and "Etiology of atrioventricular block", section on 'Familial disease'.)
Cardiac ion channels and currents — Ions (sodium, potassium, chloride and calcium) flow through the cardiac membrane in channels with pores formed by proteins encoded by specific genes . The pore-forming protein is called the alpha subunit, which also contains the voltage dependent sensors and gates. The currents carry specific names based upon the permeant ion and distinguishing kinetics or pharmacology. In most cases, the gene and protein underlying each current has been described and each has a distinct name (figure 1). For example, the voltage dependent sodium current (INa) flows through the protein NaV1.5 encoded by the gene SCN5A and similarly for other ion channels. Ion channels also consist of multiple subunits (usually named beta, delta, gamma, and so on) and other accessory proteins forming a macromolecular complex that regulates the current. The sodium-potassium pump and the sodium-calcium exchanger are not considered channels because they require energy to drive ions across the membrane against their gradients, but they do generate currents.
The resting potential — The normal resting potential in most myocardial cells is between 80 and 95 mV, with the cell interior negative relative to the extracellular space. The resting potential of the cell is set by the balance of inward (sodium and calcium) and outward (potassium) currents and the corresponding equilibrium potentials of these currents. In turn, the equilibrium potential for a given ion is determined by the concentrations of that ion inside and outside the cell. Using these concentrations, the equilibrium potential is calculated by the Nernst equation. As an example, potassium ion concentrations are higher inside than outside the cell, and the potassium equilibrium potential is between -80 and -95 mV. When potassium channels open, potassium ions flow down their gradient as an outward current, carrying positive ions outside the cell and taking the cell toward more negative potentials.
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