Cardiovascular scientists in the USA have identified in mouse models a protein known as Purkinje cell protein-4 (Pcp4) as a regulator of the heart’s rhythm. Additionally, they have found that when the Pcp4 gene is disrupted, it can cause ventricular arrhythmias.
“This study demonstrates that Pcp4 is not only important in maintaining the heart’s normal rhythmic behaviour, but that when Pcp4 expression is reduced, it short-circuits electrical activity in a small but critical population of cells in the heart muscle, leading to cardiac arrhythmias,” says Glenn I Fishman, William Goldring professor of Medicine and director of the Leon H Charney Division of Cardiology at NYU Langone, New York, USA. “We see increased morbidity and mortality when Pcp4 expression is abnormal in our animal models, including ventricular arrhythmias and sudden cardiac death.”
The results from this animal study were recently published in The Journal of Clinical Investigation.
Using mouse models of cardiomyopathy and fluorescent tags, researchers were able to isolate cardiac Purkinje cells and show that Pcp4 expression was down-regulated in the diseased hearts, producing electrical abnormalities that increased their susceptibility to arrhythmias. Investigators also found Pcp4 in cardiac ganglia, where it also influences the heart’s rhythm and modulates heart rate control. “Now that we know that Pcp4 is an important regulator of the heart’s rhythm, it could serve as an important drug target for treating arrhythmias,” adds Fishman, who is also the study’s senior author.
“Although much work remains to be done, our data suggest that drugs that mimic Pcp4’saction in the heart could potentially stabilise the heart’s rhythm.”
The NYU Langone research team believes that with better understanding of the molecular behaviour underpinning arrhythmias, more targeted drugs are on the horizon.
Eugene E. Kim and Akshay Shekhar led the study. Jia Lu, Xianming Lin, Fang-Yu Liu, Jie Zhang, and Mario Delmar were additional study co-authors.
This work was supported by grants from the National Institutes of Health (NIH).