Dependency of myocardial function on gap junction conductance

Abstract

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)]