title: Cardiomyocyte Ca2+ overload in atrial tachycardia: is blockade of L-type Ca2+ channels a promising approach to prevent electrical remodeling and arrhythmogenesis?
abstract: Electrical remodeling paradigm has important implications for the understanding of atrial fibrillation (AF) and improvement of current treatment. Cardiomyocyte Ca(2+) overload is generally accepted as the initiating signal for the tachycardia-induced changes in atrial electrical properties (electrical remodeling). The precise role of cardiomyocyte Ca(2+) overload in AF-related ion channel alterations that contribute to AF maintenance is not fully understood. Clinically, patients with AF are often treated with Ca(2+) channel blockers such as verapamil to control their ventricular rate and to improve the success rate of cardioversion procedures. However, verapamil may produce an increased L-type Ca(2+) channel current (I(Ca,L)) that may reinforce Ca(2+) overload thereby promoting AF in the atrium. Ca(2+) channel blockers which target T-type Ca(2+) channels in addition to I(Ca,L) (for instance, efonidipine) may be more efficient at preventing Ca(2+) overload and arrhythmogenic electrical remodeling, but the potential benefits of these drugs have usually been tested in experimental models where drug administration preceded the initiation of electrical remodeling. Studies in animal models with established atrial tachycardia remodeling and in patients with AF are clearly warranted to prove the efficacy of Ca(2+) channel blockers that additionally target T-type Ca(2+) channels.
authors.affiliation: Department of Pharmacology and Toxicology, Dresden University of Technology, Fetscherstr. 74, 01307, Dresden, Germany. dobrev@rcs.urz.tu-dresden.de
authors.forename: Dobromir
authors.initials: D
authors.lastname: Dobrev
mesh_terms: D000818:Animals; D016275:Atrial Function; D002118:Calcium / Q000502:physiology*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D020746:Calcium Channels, L-Type / Q000502:physiology*; D006325:Heart Atria / Q000187:drug effects / Q000503:physiopathology*; D006801:Humans; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000502:physiology; D013610:Tachycardia / Q000150:complications / Q000503:physiopathology*
chemical_list: D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D002118:Calcium