Skip Navigation LinksHome > November 2011 - Volume 58 - Issue 5 > Posttranscriptional Regulation of the β2-Subunit of Cardiac...
Journal of Cardiovascular Pharmacology:
doi: 10.1097/FJC.0b013e31822a789b
Original Article

Posttranscriptional Regulation of the β2-Subunit of Cardiac L-type Ca2+ Channels by MicroRNAs During Long-term Exposure to Isoproterenol in Rats

Carrillo, Elba D. PhD; Escobar, Yesenia MS; González, German MS; Hernández, Ascención BS; Galindo, José M. BS; García, María C. PhD; Sánchez, Jorge A. PhD

Collapse Box


Introduction and Methods: The effects of long-term β-adrenergic administration on the expression levels of the cardiac L-type Ca2+ channel β2 subunit, which regulates channel trafficking and function, were characterized in adult rats.

Results: Systemic administration of isoproterenol (150 mg·kg·h−1) for 2 d led to a 50% increase in the ventricular wet weight-to-body weight ratio (mg/g) and of more than two-fold in the expression of actin protein. In contrast, β2 subunit protein levels decreased (down to 49%), while mRNA levels remained unchanged. Furthermore, levels of microRNAs (miRs), including miR-21 and miR-132, were upregulated (7.2 and 7.9 fold, respectively). Transfection of these miRs into HEK293 cells attenuated expression of a luciferase reporter gene controlled by a conserved 3′-untranslated region (UTR) of the β2 subunit (down to 67% and 56%, respectively). Systemic administration of isoproterenol also led to briefer intracellular Ca2+ transients during action potentials measured in isolated cardiomyocytes (down to 65%).

Conclusion: These results suggest that cardiac L-type Ca2+ channel β2 subunit protein expression may be downregulated by miRs in response to long-term activation of β-adrenergic signaling, possibly as an adaptive response in cardiac hypertrophy and sustained β-adrenergic states.

© 2011 Lippincott Williams & Wilkins, Inc.

Follow Us!


Article Tools


Article Level Metrics

Search for Similar Articles
You may search for similar articles that contain these same keywords or you may modify the keyword list to augment your search.