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Calcium ions can serve as both charge carriers and second messengers. Most cells have voltage-dependent calcium channels that control the membrane permeability to calcium. These channels at the membrane open in response to changes in membrane potential. Their activity is further modulated by phosphorylation by various kinases, such as protein kinase A and protein kinase C, and by changes in intracellular calcium concentration through the action of calcium calmodulin (Ca2+/CaM). Trimmer discusses a potential mechanism by which the expression of these channels can be regulated through an interaction with a small guanosine triphosphatase (GTPase), kir/Gem, that influences trafficking of the channels through effects on assembly with auxiliary subunits that occurs in the biosynthetic pathway.