论文部分内容阅读
For optimal function, alternative pre-mRNA splicing is an exquisite mechanism to expand Cav1.2 channel electrophysiological and pharmacological properties by diversifying the proteomic structures of the channels.Our laboratory has identified a compendium of alternatively spliced exons of the CACNA1C gene and determined the presence of at least 41 combinatorial signature Cavl.2 splicing patterns.We have more precisely separated the splicing patterns of the Cav1.2 channels into cardiac-specific and smooth muscle-specific variants.By using the heterologous HEK 293 expression system, we evaluated and compared the electrophysiological and pharmacological properties of the various splice variants with the reference wild-type Cavl.2 channel.Within the population of Cav1.2 channels, we identified a sub-population that may play a role in maintaining the vasotone of arteries or play a role in arrhythmogenesis.Now, we have generated an exon-specific knock-out mouse to directly link altered channel electrophysiological property with changes in function of the heart.Work is also on-going to relate our work with clinical samples and to evaluate whether physiological and pathological signals may regulate the choice of the use of an altematively spliced exon.