Pathophysiology and pharmacology of the cardiac "late sodium current.".
The "late sodium current" (I(NaL)) is a sustained component of the fast Na+ current of cardiac myocytes and neurons. As recently appreciated, common neurological and cardiac conditions are associated with abnormal I(NaL) enhancement, which may contribute to the pathogenesis of both electrical and contractile dysfunction. For this reason, I(NaL) has become an appealing pharmacological target, with a potentially broad range of therapeutic indications. The recent approval by the FDA of an I(NaL) blocker (ranolazine) for clinical use justifies the increased interest in I(NaL) as a pathogenic mechanism and the rapid evolution of the information concerning it. The review focuses on cardiac aspects of I(NaL) enhancement; it deals with the origin of I(NaL), with its pathophysiological role and with the consequences of its pharmacological modulation. Both basic aspects and clinical evidence are discussed.
Zaza
Antonio
A
Dipartimento di Biotecnologie e Bioscienze, Università Milano-Bicocca Milano (IT), Italy. antonio.zaza@unimib.it
Belardinelli
Luiz
L
Shryock
John C
JC
D000083:Acetanilides / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D006329:Heart Conduction System / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D008954:Models, Biological; D010879:Piperazines / Q000494:pharmacology; D000069458:Ranolazine; D012964:Sodium / Q000378:metabolism*; D026941:Sodium Channel Blockers / Q000494:pharmacology*; D015222:Sodium Channels / Q000502:physiology*
D000083:Acetanilides; D010879:Piperazines; D026941:Sodium Channel Blockers; D015222:Sodium Channels; D012964:Sodium; D000069458:Ranolazine