Ranolazine (10 μM) reduced late sodium current by 82% and significantly diminished the window current in cardiomyocytes isolated from a patient with hypertrophic cardiomyopathy.
Does ranolazine improve electrophysiologic characteristics in human cardiomyocytes isolated from a patient with hypertrophic cardiomyopathy?
Ranolazine reduces augmented late sodium current and prolonged action potential duration in human HCM cardiomyocytes, suggesting a potential therapeutic role for arrhythmogenesis in HCM.
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. CONCLUSION: 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.
Barajas-Martínez et al. (Tue,) conducted a other in Hypertrophic cardiomyopathy (n=1). Ranolazine vs. Baseline / healthy controls was evaluated on Action potential duration and sodium channel current characteristics. Ranolazine (10 μM) reduced late sodium current by 82% and significantly diminished the window current in cardiomyocytes isolated from a patient with hypertrophic cardiomyopathy.