title: Numerical analysis of Ca2+ depletion in the transverse tubular system of mammalian muscle.
abstract: 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 (I(Ca)), we have combined experimental measurements of I(Ca) with quantitative numerical simulations of Ca2+ depletion. I(Ca) 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 I(Ca) decline measured in isotonic physiological solution under voltage clamp conditions.
authors.affiliation: Institute of Physiology and Pathophysiology, Medical Biophysics, University of Heidelberg, INF 326, D-69120 Heidelberg, Germany.
authors.forename: O
authors.initials: O
authors.lastname: Friedrich
authors.forename: T
authors.initials: T
authors.lastname: Ehmer
authors.forename: D
authors.initials: D
authors.lastname: Uttenweiler
authors.forename: M
authors.initials: M
authors.lastname: Vogel
authors.forename: P H
authors.initials: PH
authors.lastname: Barry
authors.forename: R H
authors.initials: RH
authors.lastname: Fink
mesh_terms: D000818:Animals; D055592:Biophysical Phenomena; D001703:Biophysics; D002118:Calcium / Q000378:metabolism*; D020746:Calcium Channels, L-Type / Q000737:chemistry; D002462:Cell Membrane; D004594:Electrophysiology; D006863:Hydrogen-Ion Concentration; D008564:Membrane Potentials; D051379:Mice; D008807:Mice, Inbred BALB C; D008954:Models, Biological; D015233:Models, Statistical; D008962:Models, Theoretical; D018485:Muscle Fibers, Skeletal / Q000737:chemistry; D018657:Muscle Fibers, Slow-Twitch / Q000737:chemistry; D009132:Muscles / Q000737:chemistry*; D018408:Patch-Clamp Techniques; D013997:Time Factors
chemical_list: D020746:Calcium Channels, L-Type; D002118:Calcium