Preservation of cardiomyocytes from the adult heart

Abstract:

Cardiomyocytes represent one of the most useful models to conduct cardiac research. A single adult heart yields millions of cardiomyocytes, but these cells do not survive for long after isolation. We aimed to determine whether inhibition of myosin II ATPase that is essential for muscle contraction may preserve fully differentiated adult cardiomyocytes. Using inhibitors of the myosin II ATPase, blebbistatin and N-benzyl-p-toluene sulphonamide (BTS), we preserved freshly isolated fully differentiated adult primary cardiomyocytes that were stored at a refrigerated temperature. Specifically, preserved cardiomyocytes stayed viable for a 2-week period with a stable expression of cardiac genes and retained the expression of key markers characteristic of cardiomyocytes. Furthermore, voltage-clamp, action potential, calcium transient and contractility studies confirmed that the preserved cardiomyocytes are comparable to freshly isolated cells. Long-term exposure of preserved cardiomyocytes to four tyrosine kinase inhibitors, sunitinib malate, dasatinib, sorafenib tosylate and imatinib mesylate, revealed their potential to induce cardiac toxicity that was manifested with a decrease in contractility and induction of cell death, but this toxicity was not observed in acute experiments conducted over the time course amenable to freshly prepared cardiomyocytes. This study introduces the concept that the inhibition of myosin II ATPase safeguards the structure and function of fully differentiated adult cardiomyocytes. The fact that these preserved cardiomyocytes can be used for numerous days after preparation makes them a robust and versatile tool in cardiac research and allows the investigation of long-term exposure to novel drugs on cardiomyocyte function.

 

Read more here: Abi-Gerges N, Pointon A, Pullen GF, Morton MJ, Oldman KL, Armstrong D, Valentin JP, Pollard CE (2013) Preservation of cardiomyocytes from the adult heart. J Mol Cell Cardiol. Nov;64:108-19.

By |2018-06-20T16:53:12+00:00November 20th, 2013|Ion Channels, Publications|Comments Off on Preservation of cardiomyocytes from the adult heart

About the Author:

Dr Michael Morton, PhD, Director and Cofounder, ApconiX, UK, an integrated toxicology and ion channel company that brings together a team of world-renowned nonclinical safety experts with over 400 years of drug discovery and development experience. Mike graduated from the University of Wolverhampton with a degree in Biomedical Sciences and then aspiration to work in hospital pathology. Having finished his Sandwich placement in Clinical Biochemistry at Sandwell Hospital and Mike subsequently gained a MSc in Clinical Biochemistry from the University of Manchester and carried out research into porphyrin metabolism. Moving to the University of Leeds, Mike completed his PhD in Pharmacology at researching adenosine receptor expression in the rat kidney . Mike was introduced to ion channels as a Post-Doc at Leeds and Yale University, patching with the likes of Fred Sigworth and Steve Hebert, then joined the Global Ion Channel Initiative at AstraZeneca. Mike worked at AstraZeneca for eight years before founding ApconiX with Professor Ruth Roberts and Dr Richard Knight. Mike has a serious passion for ion channels. And he’s very good at them . He is a serious scientist (with a serious sense of humour) who wants to make sure that every customer understands the consequences of the results he obtains and works with his colleagues to ensure a better decision is made on drug safety.