The IQ Motif is Crucial for Cav1.1 Function

Abstract EN

Ca2+-dependent modulation via calmodulin, with consensus CaM-binding IQ motif playing a key role, has been documented for most high-voltage-activated Ca2+ channels.

The skeletal muscle Cav1.1 also exhibits Ca2+-/CaM-dependent modulation.

Here, whole-cell Ca2+ current, Ca2+ transient, and maximal, immobilization-resistant charge movement (Qmax) recordings were obtained from cultured mouse myotubes, to test a role of IQ motif in function of Cav1.1.

The effect of introducing mutation (IQ to AA) of IQ motif into Cav1.1 was examined.

In dysgenic myotubes expressing YFP-Cav1.1AA, neither Ca2+ currents nor evoked Ca2+ transients were detectable.

The loss of Ca2+ current and excitation-contraction coupling did not appear to be a consequence of defective trafficking to the sarcolemma.

The Qmax in dysgenic myotubes expressing YFP-Cav1.1AA was similar to that of normal myotubes.

These findings suggest that the IQ motif of the Cav1.1 may be an unrecognized site of structural and functional coupling between DHPR and RyR.