In the cardiomyocyte nucleus, Cx43 and Cav1.2 are regulated at multiple levels of gene expression such as chromatin remodeling, alternative promoter usage, tissue-specific transcription, and alternative splicing. Once the channel proteins are translated and packaged into vesicles, they exit the Golgi and are trafficked toward specific and distinct domains of the cell surface, in particular the intercalated disk for Cx43 and T-tubules for Cav1.2. This directed targeting process is dependent on microtubules as well as the actin cytoskeleton machinery. Key proteins that provide specificity in channel trafficking are highlighted.