title: The IQ motif is crucial for Cav1.1 function.
abstract: Ca(2+)-dependent modulation via calmodulin, with consensus CaM-binding IQ motif playing a key role, has been documented for most high-voltage-activated Ca(2+) channels. The skeletal muscle Ca(v)1.1 also exhibits Ca(2+)-/CaM-dependent modulation. Here, whole-cell Ca(2+) current, Ca(2+) transient, and maximal, immobilization-resistant charge movement (Q(max)) recordings were obtained from cultured mouse myotubes, to test a role of IQ motif in function of Ca(v)1.1. The effect of introducing mutation (IQ to AA) of IQ motif into Ca(v)1.1 was examined. In dysgenic myotubes expressing YFP-Ca(v)1.1(AA), neither Ca(2+) currents nor evoked Ca(2+) transients were detectable. The loss of Ca(2+) current and excitation-contraction coupling did not appear to be a consequence of defective trafficking to the sarcolemma. The Q(max) in dysgenic myotubes expressing YFP-Ca(v)1.1(AA) was similar to that of normal myotubes. These findings suggest that the IQ motif of the Ca(v)1.1 may be an unrecognized site of structural and functional coupling between DHPR and RyR.
authors.affiliation: Department of Biophysics, P. J. Šafárik University, Košice 04001, Slovakia. katarina.stroffekova@upjs.sk
authors.forename: Katarina
authors.initials: K
authors.lastname: Stroffekova
mesh_terms: D020816:Amino Acid Motifs / Q000235:genetics*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020746:Calcium Channels, L-Type / Q000235:genetics / Q000378:metabolism*; D002147:Calmodulin / Q000378:metabolism; D018929:Cell Culture Techniques; D016384:Consensus Sequence / Q000235:genetics; D008564:Membrane Potentials / Q000502:physiology; D051379:Mice; D018485:Muscle Fibers, Skeletal / Q000166:cytology* / Q000378:metabolism*; D009154:Mutation / Q000235:genetics; D018408:Patch-Clamp Techniques; D017434:Protein Structure, Tertiary; D019837:Ryanodine Receptor Calcium Release Channel / Q000378:metabolism*
chemical_list: C529218:CACNA1S protein, mouse; D020746:Calcium Channels, L-Type; D002147:Calmodulin; D019837:Ryanodine Receptor Calcium Release Channel; D002118:Calcium