title: [The late sodium current: pathophysiology and pharmacology of a new therapeutic target].
abstract: The sodium current (INa) plays a pivotal role in the propagation of electrical activity in the heart. However, a large body of evidence indicates that the "late" component of INa (INaL) may be enhanced in diseased myocardium. INaL enhancement has consequences on the electrical stability, contractile function and metabolism of cardiac myocytes, which may significantly contribute to disease progression. The possibility of blocking INaL selectively, that is to say without affecting the INa component involved in electrical propagation, has recently emerged. INaL has hence become a "therapeutic target", thus far clinically validated in the treatment of angina and arrhythmias but, as suggested by bench evidence, potentially relevant to a wider range of cardiac disorders. Such multiplicity of effects originates from the complex network of cell functions affected by INaL enhancement; acquaintance with such a network is useful in fully exploiting the therapeutic potential of selective INaL inhibition. This review deals with the pathophysiology of INaL enhancement and with the basic principles underlying its selective inhibition. Clinical evidence of antianginal and antiarrhythmic efficacy of INaL inhibition is available, but its discussion goes beyond the scope of this review.
authors.affiliation: Dipartimento di Biotecnologie e Bioscienze, Università degli Studi di Milano-Bicocca, Milano.
authors.forename: Antonio
authors.initials: A
authors.lastname: Zaza
mesh_terms: D000083:Acetanilides / Q000494:pharmacology / Q000627:therapeutic use*; D001145:Arrhythmias, Cardiac / Q000188:drug therapy / Q000503:physiopathology; D018450:Disease Progression; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D006329:Heart Conduction System / Q000187:drug effects*; D006331:Heart Diseases / Q000188:drug therapy* / Q000503:physiopathology*; D006801:Humans; D032342:Muscle Cells / Q000187:drug effects / Q000378:metabolism; D009200:Myocardial Contraction / Q000187:drug effects; D017202:Myocardial Ischemia / Q000188:drug therapy / Q000503:physiopathology; D010879:Piperazines / Q000494:pharmacology / Q000627:therapeutic use*; D000069458:Ranolazine; D012964:Sodium / Q000378:metabolism*; D015222:Sodium Channels / Q000187:drug effects; D016896:Treatment Outcome
chemical_list: D000083:Acetanilides; D004791:Enzyme Inhibitors; D010879:Piperazines; D015222:Sodium Channels; D012964:Sodium; D000069458:Ranolazine