This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kasielke, N. Articles by Flucher, B. E. Search for Related Content PubMed PubMed Citation Articles by Kasielke, N. Articles by Flucher, B. E.

Cardiac-type EC-Coupling in Dysgenic Myotubes Restored with Ca²⁺ Channel Subunit Isoforms _1C and _1D Does not Correlate with Current Density

Nicole Kasielke ^*, Gerald J. Obermair , Gerlinde Kugler ^*, Manfred Grabner ^* and Bernhard E. Flucher ^* 

^* Department of Biochemical Pharmacology and Department of Physiology, University of Innsbruck, A-6020 Innsbruck, Austria

Correspondence: Address reprint requests to Dr. Bernhard E. Flucher, Dept. of Physiology, University of Innsbruck, Fritz-Pregl-Str. 3, A-6020 Innsbruck, Austria. Tel.: +43-512-507-3787; Fax: +43-512-507-2836; E-mail: bernhard.e.flucher{at}uibk.ac.at.

Ca²⁺-induced Ca²⁺-release (CICR)—the mechanism of cardiac excitation-contraction (EC) coupling—also contributes to skeletal muscle contraction; however, its properties are still poorly understood. CICR in skeletal muscle can be induced independently of direct, calcium-independent activation of sarcoplasmic reticulum Ca²⁺ release, by reconstituting dysgenic myotubes with the cardiac Ca²⁺ channel _1C (Ca_V1.2) subunit. Ca²⁺ influx through _1C provides the trigger for opening the sarcoplasmic reticulum Ca²⁺ release channels. Here we show that also the Ca²⁺ channel _1D isoform (Ca_V1.3) can restore cardiac-type EC-coupling. GFP-_1D expressed in dysgenic myotubes is correctly targeted into the triad junctions and generates action potential-induced Ca²⁺ transients with the same efficiency as GFP-_1C despite threefold smaller Ca²⁺ currents. In contrast, GFP-_1A, which generates large currents but is not targeted into triads, rarely restores action potential-induced Ca²⁺ transients. Thus, cardiac-type EC-coupling in skeletal myotubes depends primarily on the correct targeting of the voltage-gated Ca²⁺ channels and less on their current size. Combined patch-clamp/fluo-4 Ca²⁺ recordings revealed that the induction of Ca²⁺ transients and their maximal amplitudes are independent of the different current densities of GFP-_1C and GFP-_1D. These properties of cardiac-type EC-coupling in dysgenic myotubes are consistent with a CICR mechanism under the control of local Ca²⁺ gradients in the triad junctions.

This article has been cited by other articles:

				S. A. Goonasekera, S. R. W. Chen, and R. T. Dirksen Reconstitution of local Ca2+ signaling between cardiac L-type Ca2+ channels and ryanodine receptors: insights into regulation by FKBP12.6 Am J Physiol Cell Physiol, December 1, 2005; 289(6): C1476 - C1484. [Abstract] [Full Text] [PDF]

				L. Carbonneau, D. Bhattacharya, D. C. Sheridan, and R. Coronado Multiple Loops of the Dihydropyridine Receptor Pore Subunit Are Required for Full-Scale Excitation-Contraction Coupling in Skeletal Muscle Biophys. J., July 1, 2005; 89(1): 243 - 255. [Abstract] [Full Text] [PDF]

				H. Takekura, C. Paolini, C. Franzini-Armstrong, G. Kugler, M. Grabner, and B. E. Flucher Differential Contribution of Skeletal and Cardiac II-III Loop Sequences to the Assembly of Dihydropyridine-Receptor Arrays in Skeletal Muscle Mol. Biol. Cell, December 1, 2004; 15(12): 5408 - 5419. [Abstract] [Full Text] [PDF]

				R. G. Weiss, K. M. S. O'Connell, B. E. Flucher, P. D. Allen, M. Grabner, and R. T. Dirksen Functional analysis of the R1086H malignant hyperthermia mutation in the DHPR reveals an unexpected influence of the III-IV loop on skeletal muscle EC coupling Am J Physiol Cell Physiol, October 1, 2004; 287(4): C1094 - C1102. [Abstract] [Full Text] [PDF]

				J. M. Eltit, J. Hidalgo, J. L. Liberona, and E. Jaimovich Slow Calcium Signals after Tetanic Electrical Stimulation in Skeletal Myotubes Biophys. J., May 1, 2004; 86(5): 3042 - 3051. [Abstract] [Full Text] [PDF]

				A. Shtifman, C. Paolini, J. R. Lopez, P. D. Allen, and F. Protasi Ca2+ influx through {alpha}1S DHPR may play a role in regulating Ca2+ release from RyR1 in skeletal muscle Am J Physiol Cell Physiol, January 1, 2004; 286(1): C73 - C78. [Abstract] [Full Text] [PDF]