Send to

Choose Destination
Life Sci. 2009 Feb 13;84(7-8):250-6. doi: 10.1016/j.lfs.2008.12.007. Epub 2008 Dec 14.

Mechanisms of alpha1-adrenoceptor mediated QT prolongation in the diabetic rat heart.

Author information

National Standard Laboratory of Pharmacology for Chinese Materia Medica, Research Center of Acupuncture and Pharmacology, Nanjing University of Chinese Medicine, Nanjing 210029, China.



Diabetes mellitus is associated with changes of alpha(1)-adrenoceptor (alpha(1)-AR) on heart electrical function and expression. In this study, we investigated the ionic basis underlying abnormal alpha(1)-AR mediated QT prolongation in the diabetic rat hearts.


Electrophysiological and biochemical techniques were used in Streptozotocin (STZ)-induced diabetic and control rat hearts.


In both control and diabetic rats, the alpha(1)-AR agonist, phenylephrine (PE, 10-100 microM) prolonged the rate-corrected QT intervals (QTc) and action potential durations at 30% (APD(30)) and 90% (APD(90)) repolarization levels with the increased QTc and APD(90) significantly greater in diabetic rats. PE significantly decreased the transient outward K(+) current (I(to)) and the steady-state K(+) current (I(ss)) in both control and diabetic rats but had no effects on the delayed rectifier K(+) current (I(k)). However, PE induced a greater reduction mainly in the I(ss), but not I(to), in diabetic rats. Furthermore, using RT-PCR and Western blot analyses, we found that alpha(1A)-ARs were over-expressed in the left ventricular tissues of the diabetic rat hearts at both the mRNA and the protein levels.


These data suggested that in diabetic hearts, a greater sensitivity of the alpha(1A)-AR mediated the larger suppression of I(ss) and resulted in a more prolonged APD(90) and QTc. Thus, higher alpha(1A)-AR expression levels in diabetic heart may underlie this type of diabetic cardiomyopathy and suggests that alpha(1A)-AR may serve as a therapeutic target.

[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center