BackgroundHypertrophic 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.MethodsCardiomyocytes 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 (I-Na) characteristics.ResultsAction 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 M). Whole cell patch-clamp recording yielded robust peak I-Na and large late I-Na (1.1% of peak I-Na vs 0.1-0.2% in healthy controls). A large window current was observed as well. Ranolazine (10 M) shifted steady-state V-0.5 of inactivation by -8 mV, reduced late I-Na by 82%, and significantly diminished the window current.ConclusionOur 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 I-Na and thus to reduce the prolonged APD in the setting of HCM. These results suggest a potential therapeutic role for ranolazine in HCM.