title: Roles of subcellular Na+ channel distributions in the mechanism of cardiac conduction.
abstract: The gap junction and voltage-gated Na(+) channel play an important role in the action potential propagation. The purpose of this study was to elucidate the roles of subcellular Na(+) channel distribution in action potential propagation. To achieve this, we constructed the myocardial strand model, which can calculate the current via intercellular cleft (electric-field mechanism) together with gap-junctional current (gap-junctional mechanism). We conducted simulations of action potential propagation in a myofiber model where cardiomyocytes were electrically coupled with gap junctions alone or with both the gap junctions and the electric field mechanism. Then we found that the action potential propagation was greatly affected by the subcellular distribution of Na(+) channels in the presence of the electric field mechanism. The presence of Na(+) channels in the lateral membrane was important to ensure the stability of propagation under conditions of reduced gap-junctional coupling. In the poorly coupled tissue with sufficient Na(+) channels in the lateral membrane, the slowing of action potential propagation resulted from the periodic and intermittent dysfunction of the electric field mechanism. The changes in the subcellular Na(+) channel distribution might be in part responsible for the homeostatic excitation propagation in the diseased heart.
authors.affiliation: The Center for Advanced Medical Engineering and Informatics, Osaka University, Osaka, Japan. Electronic address: tsumoto@pharma2.med.osaka-u.ac.jp.
authors.forename: Kunichika
authors.initials: K
authors.lastname: Tsumoto
authors.affiliation: Department of Cardiovascular and Respiratory Medicine, Heart Rhythm Center, Shiga University of Medical Science, Shiga, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Ashihara
authors.affiliation: Laboratory of Biomedical Science and Information Management, Research Institute, National Cerebral and Cardiovascular Center, Osaka, Japan.
authors.forename: Ryo
authors.initials: R
authors.lastname: Haraguchi
authors.affiliation: Laboratory of Biomedical Science and Information Management, Research Institute, National Cerebral and Cardiovascular Center, Osaka, Japan.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Nakazawa
authors.affiliation: Division of Molecular and Cellular Pharmacology, Department of Pharmacology, Graduate School of Medicine, Osaka University, Osaka, Japan; The Center for Advanced Medical Engineering and Informatics, Osaka University, Osaka, Japan. Electronic address: ykurachi@pharma2.med.osaka-u.ac.jp.
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Kurachi
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000818:Animals; D002415:Cats; D048429:Cell Size; D017629:Gap Junctions / Q000502:physiology; D006329:Heart Conduction System / Q000166:cytology / Q000378:metabolism*; D008955:Models, Cardiovascular; D009206:Myocardium / Q000166:cytology / Q000378:metabolism; D015222:Sodium Channels / Q000378:metabolism*; D013347:Subcellular Fractions / Q000378:metabolism
chemical_list: D015222:Sodium Channels