| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
* Joint Graduate Program in Biomedical Engineering, The University of Memphis, and The University of Tennessee Health Science Center, Memphis, Tennessee USA and Department of Physiology and Biophysics, The University of Calgary, Calgary, Canada
Correspondence: Address reprint requests to Semahat S. Demir, PhD, Dept. of Biomedical Engineering, University of Memphis, 330 Engineering Technology Building, Memphis, TN 38152-3210. Tel.: 901-678-3170; Fax: 901-678-5281; E-mail: sdemir{at}memphis.edu.
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.
This article has been cited by other articles:
 |
|
 |
|
  C. Fiset and W. R. Giles Transmural Gradients of Repolarization and Excitation-Contraction Coupling in Mouse Ventricle Circ. Res., May 26, 2006; 98(10): 1237 - 1239. [Full Text] [PDF]
|
|
|
|
 |
|
 F. C Howarth, M Jacobson, M Shafiullah, and E Adeghate Long-term effects of streptozotocin-induced diabetes on the electrocardiogram, physical activity and body temperature in rats Exp Physiol, November 1, 2005; 90(6): 827 - 835. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. V. Tranquillo, J. Hlavacek, and C. S. Henriquez An integrative model of mouse cardiac electrophysiology from cell to torso Europace, January 1, 2005; 7(s2): S56 - S70. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. L. Winslow and J. L. Greenstein The Ongoing Journey to Understand Heart Function Through Integrative Modeling Circ. Res., December 10, 2004; 95(12): 1135 - 1136. [Full Text] [PDF]
|
|
|
|
 |
|
 T. R. Shannon, F. Wang, J. Puglisi, C. Weber, and D. M. Bers A Mathematical Treatment of Integrated Ca Dynamics within the Ventricular Myocyte Biophys. J., November 1, 2004; 87(5): 3351 - 3371. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Raimondi, P. De Paoli, E. Mannucci, G. Lonardo, L. Sartiani, G. Banchelli, R. Pirisino, A. Mugelli, and E. Cerbai Restoration of Cardiomyocyte Functional Properties by Angiotensin II Receptor Blockade in Diabetic Rats Diabetes, July 1, 2004; 53(7): 1927 - 1933. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Rosati and D. McKinnon Regulation of Ion Channel Expression Circ. Res., April 16, 2004; 94(7): 874 - 883. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
