Disrupting Calcium Channel Expression To Lower Blood Pressure: New Targeting of a Well-Known Channel

Molecular interventions to reduce the expression of functional Ca_V1.2 channels. A. The co-assembly of α-β complexes in the endoplasmic reticulum (ER) permits translocation of Ca_V1.2 channels to the plasma membrane to form functional channels. B. Overexpressed mutant β subunits co-assemble in the ER with the α _1C subunit but prevent its translocation to the plasma membrane. These “decoy” β subunits retain the BID that permits interaction with the AID of the α subunit, but lack the ability to mask the ER retention signal to enable exit of the α-β complex from the ER. C. Overexpression of the AID of the α _1C subunit acts as bait for the BID of endogenous β subunits, thereby reducing their availability to bind to endogenous α _1C to permit its exit from the ER.