title: Electrophysiologic characteristics and pharmacologic response of human cardiomyocytes isolated from a patient with hypertrophic cardiomyopathy.
abstract: BACKGROUND
  Hypertrophic cardiomyopathy (HCM) is the most common monogenic cardiac disorder encountered in the clinic. Data relative to the electrophysiologic characteristics and pharmacologic responsiveness of human tissues and cells isolated from patients with HCM are rare. As a consequence, cellular mechanisms underlying arrhythmogenicity are poorly understood.
  
  
  METHODS
  Cardiomyocytes were enzymatically dissociated from a septal myectomy surgically removed from a patient with obstructive HCM. Sharp microelectrodes and patch-clamp techniques were used to evaluate action potential and sodium channel current (INa ) characteristics.
  
  
  RESULTS
  Action potential morphology recorded was typical of an M cell, but with a longer than normal duration (APD) and a relatively steep APD-rate relationship. APD at all rates was significantly reduced following exposure to ranolazine (10 μM). Whole cell patch-clamp recording yielded robust peak INa and large late INa (1.1% of peak INa vs 0.1-0.2% in healthy controls). A large window current was observed as well. Ranolazine (10 μM) shifted steady-state V0.5 of inactivation by -8 mV, reduced late INa by 82%, and significantly diminished the window current.
  
  
  CONCLUSIONS
  Our results indicate the presence of cells with M-cell characteristics in the septum of the human heart, as has previously been described in the canine heart. They also point to an ameliorative effect of ranolazine to reduce augmented late INa and thus to reduce the prolonged APD in the setting of HCM. These results suggest a potential therapeutic role for ranolazine in HCM.
authors.affiliation: Department of Molecular Genetics and Experimental Cardiology, Masonic Medical Research Laboratory, Utica, New York.
authors.forename: Hector
authors.initials: H
authors.lastname: Barajas-Martínez
authors.forename: Dan
authors.initials: D
authors.lastname: Hu
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Goodrow
authors.forename: Frederic
authors.initials: F
authors.lastname: Joyce
authors.forename: Charles
authors.initials: C
authors.lastname: Antzelevitch
mesh_terms: D000083:Acetanilides / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects; D002312:Cardiomyopathy, Hypertrophic / Q000473:pathology / Q000503:physiopathology*; D002478:Cells, Cultured; D006339:Heart Rate; D006801:Humans; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D010879:Piperazines / Q000494:pharmacology; D000069458:Ranolazine; D012964:Sodium / Q000378:metabolism*; D026941:Sodium Channel Blockers / Q000494:pharmacology
chemical_list: D000083:Acetanilides; D010879:Piperazines; D026941:Sodium Channel Blockers; D012964:Sodium; D000069458:Ranolazine
keywords: M cell; action potential; arrhythmia; ranolazine; sodium channel current