PMID:15536090

Citation	Obermair, GJ, Kugler, G, Baumgartner, S, Tuluc, P, Grabner, M and Flucher, BE (2005) The Ca2+ channel alpha2delta-1 subunit determines Ca2+ current kinetics in skeletal muscle but not targeting of alpha1S or excitation-contraction coupling. J. Biol. Chem. 280:2229-37
Abstract	Auxiliary channel subunits regulate membrane expression and modulate current properties of voltage-activated Ca(2+) channels and thus are involved in numerous important cell functions, including muscle contraction. Whereas the importance of the alpha(1S), beta(1a), and gamma Ca(2+) channel subunits in skeletal muscle has been determined by using null-mutant mice, the role of the alpha(2)delta-1 subunit in skeletal muscle is still elusive. We addressed this question by small interfering RNA silencing of alpha(2)delta-1 in reconstituted dysgenic (alpha(1S)-null) myotubes and in BC3H1 skeletal muscle cells. Immunofluorescence labeling of the alpha(1S) and alpha(2)delta-1 subunits and whole cell patch clamp recordings demonstrated that triad targeting and functional expression of the skeletal muscle Ca(2+) channel were not compromised by the depletion of the alpha(2)delta-1 subunit. The amplitudes and voltage dependences of L-type Ca(2+) currents and of the depolarization-induced Ca(2+) transients were identical in control and in alpha(2)delta-1-depleted muscle cells. However, alpha(2)delta-1 depletion significantly accelerated the current kinetics, most likely by the conversion of slowly activating into fast activating Ca(2+) channels. Reverse transcription-PCR analysis indicated that alpha(2)delta-1 is the exclusive isoform expressed in differentiated BC3H1 cells and that depletion of alpha(2)delta-1 was not compensated by the up-regulation of any other alpha(2)delta isoform. Thus, in skeletal muscle the Ca(2+) channel alpha(2)delta-1 subunit functions as a major determinant of the characteristic slow L-type Ca(2+) current kinetics. However, this subunit is not essential for targeting of Ca(2+) channels or for their primary physiological role in activating skeletal muscle excitation-contraction coupling.
Links	PubMed Online version:10.1074/jbc.M411501200
Keywords	Animals; Calcium Channels/physiology; Cell Line; Fluorescent Antibody Technique; Kinetics; Mice; Mice, Mutant Strains; Molecular Sequence Data; Muscle, Skeletal/physiology; Patch-Clamp Techniques; Plasmids; RNA, Small Interfering/metabolism
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