Workshop on Computational Physiology

Conduction velocity in the heart is dependent on two main factors: intercellular electrical coupling and cellular electrical excitability. There is significant redundancy, “conduction reserve”, in these parameters such that significant reduction in the conduction velocity of the action potential requires either a large change in one of these parameters or combined changes in both. We have used optical mapping to measure conduction velocity in hearts from streptozotocin-induced diabetic rats. Our results show little change in baseline conduction velocity in diabetic hearts compared to controls. However, both the gap junction uncoupler heptanol (0.5-1 mM), and elevated extracellular potassium (9 mM) produced a significantly greater reduction of conduction velocity in diabetic hearts than in controls. Immunofluorescent labeling of connexin-43 showed significant gap junction reorganization in diabetic hearts, such that an abnormally large fraction of the Cx-43 fluorescence was observed along the sides of the cells. We hypothesize that this process, known as lateralization of connexins, results in reduced intercellular coupling. Depending on whether the lateralized connexins are functional or not, this process may also result in changes in the anisotropy of conduction in the ventricular tissue.