title: Larger late sodium current density as well as greater sensitivities to ATX II and ranolazine in rabbit left atrial than left ventricular myocytes.
abstract: An increase of cardiac late sodium current (INa.L) is arrhythmogenic in atrial and ventricular tissues, but the densities of INa.L and thus the potential relative contributions of this current to sodium ion (Na(+)) influx and arrhythmogenesis in atria and ventricles are unclear. In this study, whole-cell and cell-attached patch-clamp techniques were used to measure INa.L in rabbit left atrial and ventricular myocytes under identical conditions. The density of INa.L was 67% greater in left atrial (0.50 ± 0.09 pA/pF, n = 20) than in left ventricular cells (0.30 ± 0.07 pA/pF, n = 27, P < 0.01) when elicited by step pulses from -120 to -20 mV at a rate of 0.2 Hz. Similar results were obtained using step pulses from -90 to -20 mV. Anemone toxin II (ATX II) increased INa.L with an EC50 value of 14 ± 2 nM and a Hill slope of 1.4 ± 0.1 (n = 9) in atrial myocytes and with an EC50 of 21 ± 5 nM and a Hill slope of 1.2 ± 0.1 (n = 12) in ventricular myocytes. Na(+) channel open probability (but not mean open time) was greater in atrial than in ventricular cells in the absence and presence of ATX II. The INa.L inhibitor ranolazine (3, 6, and 9 μM) reduced INa.L more in atrial than ventricular myocytes in the presence of 40 nM ATX II. In summary, rabbit left atrial myocytes have a greater density of INa.L and higher sensitivities to ATX II and ranolazine than rabbit left ventricular myocytes.
authors: Cardio-Electrophysiological Research Laboratory, Medical College of Wuhan University of Science and Technology, Wuhan, China;
authors: Antao
authors: A
authors: Luo
authors: Jihua
authors: J
authors: Ma
authors: Yejia
authors: Y
authors: Song
authors: Chunping
authors: C
authors: Qian
authors: Ying
authors: Y
authors: Wu
authors: Peihua
authors: P
authors: Zhang
authors: Leilei
authors: L
authors: Wang
authors: Chen
authors: C
authors: Fu
authors: Zhenzhen
authors: Z
authors: Cao
authors: John C
authors: JC
authors: Shryock
mesh_terms: D000083:Acetanilides / Q000494:pharmacology*; D000200:Action Potentials; D000818:Animals; D003064:Cnidarian Venoms / Q000494:pharmacology*; D006325:Heart Atria / Q000166:cytology*; D006352:Heart Ventricles / Q000166:cytology*; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D009928:Organ Specificity; D010879:Piperazines / Q000494:pharmacology*; D011817:Rabbits; D000069458:Ranolazine; D012964:Sodium / Q000378:metabolism*; D026941:Sodium Channel Blockers / Q000494:pharmacology*
chemical_list: D000083:Acetanilides; D003064:Cnidarian Venoms; D010879:Piperazines; D026941:Sodium Channel Blockers; C028800:toxin II (Anemonia sulcata); D012964:Sodium; D000069458:Ranolazine
keywords: cardiomyocyte; late sodium current; patch-clamp technique; regional differences