Aims: 

The Ca _v1.2 L-type calcium channel is involved in a large number of diverse functions such as the contraction of cardiac and smooth muscle, the release of hormones and the regulation of enzymatic activities. The purpose of our studies was to investigate the general role of the Ca_v1.2 L-type channel in vascular smooth muscle cells and to characterize the interaction between Ca_v1.2 and BK_Ca-channels.

Methods: 

Since Ca _v1.2 L-type (-/-) mice die in utero, we used the tamoxifen-inducible Cre/loxP recombination system to inactivate the Ca _v1.2 gene specifically in smooth muscle cells. The interaction between Ca _v1.2 and BK_Ca-channel proteins was investigated using the yeast two hybrid split ubiquitin system.

Results: 

The tissue specific deletion of Ca _v1.2 in the vascular smooth muscle revealed its dominant role _v for blood pressure regulation and its requirement for the autoregulation and maintenance of the vascular tone in response to depolarization and pressure. The unique large-conductance, voltage- and Ca²⁺ -activated K⁺ (BK) channel limits the Ca²⁺ entry and thereby arterial contraction by repolarizing smooth muscle cells and closing of L-type channels. Several studies indicated that BK_Ca and L-type calcium channels are co-localized and functionally associated in the smooth muscle cell membrane. Using the yeast two hybrid split ubiquitin system we could show that both channels directly interact with each other without the need for scaffolding proteins.

Conclusion: 

These results demonstrate that Ca _v1.2 channels are crucial for the regulation of blood pressure and the development of the myogenic tone and directly interact with BK_Ca-channels within macromolecular complexes.