Ca(V)β-subunit dependence of forward and reverse trafficking of Ca(V)1.2 calcium channels

Auxiliary Ca(V)β subunits interact with the pore forming Ca(V)α(1) subunit to promote the plasma membrane expression of high voltage-activated calcium channels and to modulate the biophysical properties of Ca(2+) currents. However, the effect of Ca(V)β subunits on channel trafficking to and from the plasma membrane is still controversial. Here, we have investigated the impact of Ca(V)β1b and Ca(V)β2a subunits on plasma membrane trafficking of Ca(V)1.2 using a live-labeling strategy. We show that the Ca(V)β1b subunit is more potent in increasing Ca(V)1.2 expression at the plasma membrane than the Ca(V)β2a subunit and that this effect is not related to modification of intracellular trafficking of the channel (i.e. neither forward trafficking, nor recycling, nor endocytosis). We conclude that the differential effect of Ca(V)β subunit subtypes on Ca(V)1.2 surface expression is likely due to their differential ability to protect Ca(V)1.2 from degradation.