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Biophys J, May 2001, p. 2046-2055, Vol. 80, No. 5

Numerical Analysis of Ca2+ Depletion in the Transverse Tubular System of Mammalian Muscle

Oliver Friedrich,* Thomas Ehmer,* Dietmar Uttenweiler,*dagger Martin Vogel,* Peter H. Barry,Dagger and Rainer H. A. Fink*

 *Institute of Physiology and Pathophysiology, Medical Biophysics, University of Heidelberg, INF 326, D-69120 Heidelberg, Germany;  dagger Interdisciplinary Center for Scientific Computing, University of Heidelberg, INF 368, D-69120 Heidelberg, Germany; and  Dagger School of Physiology and Pharmacology, University of New South Wales, Sydney 2052, Australia

Calcium currents were recorded in contracting and actively shortening mammalian muscle fibers. In order to characterize the influence of extracellular calcium concentration changes in the small unstirred lumina of the transverse tubular system (TTS) on the time course of the slow L-type calcium current (ICa), we have combined experimental measurements of ICa with quantitative numerical simulations of Ca2+ depletion. ICa was recorded both in calcium-buffered and unbuffered external solutions using the two-microelectrode voltage clamp technique (2-MVC) on short murine toe muscle fibers. A simulation program based on a distributed TTS model was used to calculate the effect of ion depletion in the TTS. The experimental data obtained in a solution where ion depletion is suppressed by a high amount of a calcium buffering agent were used as input data for the simulation. The simulation output was then compared with experimental data from the same fiber obtained in unbuffered solution. Taking this approach, we could quantitatively show that the calculated Ca2+ depletion in the transverse tubular system of contracting mammalian muscle fibers significantly affects the time-dependent decline of Ca2+ currents. From our findings, we conclude that ion depletion in the tubular system may be one of the major effects for the ICa decline measured in isotonic physiological solution under voltage clamp conditions.

Biophys J, May 2001, p. 2046-2055, Vol. 80, No. 5
© 2001 by the Biophysical Society   0006-3495/01/05/2046/10  $2.00


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