Dysgenesis, muscular

Key findings that demonstrated that the 0 subunit is the essential component of L-type channels have come from studies of the channel activity of the expressed protein. Expression studies performed in mammalian liver fibroblasts have demonstrated that the oti subunit alone can form a channel [77] and contains the receptors for the DHPs, PAAs and diltiazem [64]. In very elegant studies using a mouse model of muscular dysgenesis it has been demonstrated that the ] subunit DNA can restore Ca currents and the charge movement that arises from the voltagesensing function of the channels to the mutant cells that normally lack these activities [21,78,79]. The restoration of these activities restores excitation-contraction coupling. Thus it is clear that the aj subunit is the major functional unit of L-type Ca channels. 

Figure 4. Mutations in the human Cavl.l and Cay 1.2 (L-type) voltage-gated calcium channels associated with Hypokalaemic Periodic Paralysis (HypoPP) and Timothy Syndrome (TS), respectively. Also shown is the nucleotide deletion in the mouse Cay 1.1 homolog associated with Muscular Dysgenesis...

Table 5. cacnals (Cavl.l, ctls) Functional results for mutations associated with muscular dysgenesis... 

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