The IQ motif is crucial for Ca v 1.1 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 v1.1 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 v1.1. The effect of introducing mutation (IQ to AA) of IQ motif into Ca v1.1 was examined. In dysgenic myotubes expressing YFP-Ca v1.1AA, 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 v1.1AA was similar to that of normal myotubes. These findings suggest that the IQ motif of the Ca v1.1 may be an unrecognized site of structural and functional coupling between DHPR and RyR. © 2011 Katarina Stroffekova.