A Mathematical Model of the Electrophysiological Alterations in Rat Ventricular Myocytes in Type-I Diabetes |
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| Authors: | Sandeep V Pandit Semahat S Demir |
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| Affiliation: | * Joint Graduate Program in Biomedical Engineering, The University of Memphis, and The University of Tennessee Health Science Center, Memphis, Tennessee USA
† Department of Physiology and Biophysics, The University of Calgary, Calgary, Canada |
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| Abstract: | Our mathematical model of the rat ventricular myocyte (Pandit et al., 2001) was utilized to explore the ionic mechanism(s) that underlie the altered electrophysiological characteristics associated with the short-term model of streptozotocin-induced, type-I diabetes. The simulations show that the observed reductions in the Ca2+-independent transient outward K+ current (It) and the steady-state outward K+ current (Iss), along with slowed inactivation of the L-type Ca2+ current (ICaL), can result in the prolongation of the action potential duration, a well-known experimental finding. In addition, the model demonstrates that the slowed reactivation kinetics of It in diabetic myocytes can account for the more pronounced rate-dependent action potential duration prolongation in diabetes, and that a decrease in the electrogenic Na+-K+ pump current (INaK) results in a small depolarization in the resting membrane potential (Vrest). This depolarization reduces the availability of the Na+ channels (INa), thereby resulting in a slower upstroke (dV/dtmax) of the diabetic action potential. Additional simulations suggest that a reduction in the magnitude of ICaL, in combination with impaired sarcoplasmic reticulum uptake can lead to a decreased sarcoplasmic reticulum Ca2+ load. These factors contribute to characteristic abnormal Ca2+]i homeostasis (reduced peak systolic value and rate of decay) in myocytes from diabetic animals. In combination, these simulation results provide novel information and integrative insights concerning plausible ionic mechanisms for the observed changes in cardiac repolarization and excitation-contraction coupling in rat ventricular myocytes in the setting of streptozotocin-induced, type-I diabetes. |
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