Voltage-gated, dihydropyridine-sensitive L-type Ca(2+) channels are multimeric 
proteins composed of a pore-forming transmembrane α(1) subunit (Ca(v)1.2) and 
accessory β, α(2)δ, and γ subunits. Ca(2+) entry via Ca(v)1.2 channels shapes 
the action potential (AP) of cardiac myocytes and is required for 
excitation-contraction coupling. Two de novo point mutations of Ca(v)1.2 glycine 
residues, G406R and G402S, cause a rare multisystem disorder called Timothy 
syndrome (TS). Here, we discuss recent work on the mechanisms by which Ca(v)1.2 
channels bearing TS mutations display slowed inactivation that leads to 
increased Ca(2+) influx, prolonging the cardiac AP and promoting lethal 
arrhythmias. Based on these studies, we propose a model in which the scaffolding 
protein AKAP79/150 stabilizes the open conformation of Ca(v)1.2-TS channels and 
facilitates physical interactions among adjacent channels via their C-tails, 
increasing the activity of adjoining channels and amplifying Ca(2+) influx.