ギャップジャンクション抵抗変動が心機能に及ぼす影響–京都モデルを用いたシミュレーション考察–

抄録

Myocardial gap junction is prerequisite for normal rhythmic cardiac contraction through providing an electrical pathway between neighboring cells. The conductance is voltage- and intracellular [Ca²⁺]-dependent. The aim of this study is to model the voltage- and Ca²⁺- dependent gating properties of gap junction, and to investigate the relationship between cardiac function and gap junction conductance through computer simulation. A new Ca²⁺ dependent gate was added to the voltage-dependent gate model developed by Vogel and Weingart (1998). The Ca²⁺ gating kinetics was determined based on two experimental findings: 1) Gap junction closes at the physiological concentration range of intracellular Ca²⁺ (Noma and Tsuboi, 1987), 2) Changes in the gap junction conductance is less than 10% during a twitch contraction (Weidmann, 1970). This gap junction model was used to connect 50 cell models with membrane dynamics as well as Ca²⁺-transient defined by Kyoto Model (Matsuoka et al., 2003) in a linear strand, and effects of altering gap junction conductance on cardiac function were evaluated. Lowering the gap junction conductance caused a decrease in E_max and energy efficiency along with the decrease in the conduction velocity. The results suggested that decreased gap junction conductance, under pathological conditions such as ischemia, enhances contractile dysfunction. [Jpn J Physiol 55 Suppl:S90 (2005)]