Cart (Loading....) | Create Account
Close category search window
 

Dynamic action potential clamp as a powerful tool in the development of a gene-based bio-pacemaker

Sign In

Cookies must be enabled to login.After enabling cookies , please use refresh or reload or ctrl+f5 on the browser for the login options.

Formats Non-Member Member
$31 $13
Learn how you can qualify for the best price for this item!
Become an IEEE Member or Subscribe to
IEEE Xplore for exclusive pricing!
close button

puzzle piece

IEEE membership options for an individual and IEEE Xplore subscriptions for an organization offer the most affordable access to essential journal articles, conference papers, standards, eBooks, and eLearning courses.

Learn more about:

IEEE membership

IEEE Xplore subscriptions

4 Author(s)
Verkerk, Arie O. ; Department of Physiology, Academic Medical Center, University of Amsterdam, the Netherlands ; Zegers, Jan G. ; van Ginneken, A.C.G. ; Wilders, R.

The development of a genetically engineered ‘biological pacemaker’, or ‘bio-pacemaker’, is a rapidly emerging field of research. One of the approaches in this field is to turn intrinsically quiescent myocardial cells, i.e., atrial or ventricular cells, into pacemaker cells by making them express the cardiac hyperpolarization-activated ‘pacemaker current’ If (known in neurophysiology as Ih), which is encoded by the hyperpolarization-activated cyclic nucleotide-modulated (HCN) gene family. We carried out ‘dynamic action potential clamp’ (dAPC) experiments in which we record current from a HEK-293 cell transfected with HCN4, which is the dominant HCN isoform in the sinoatrial (SA) node. This HCN4-transfected HEK-293 cell is voltage-clamped by the action potential generated in a real-time simulation of a human atrial cell (Courtemanche-Ramirez-Nattel model). In a continuous feedback loop, this current is injected into the atrial cell, so that this cell effectively expresses an HCN4-based pacemaker current. With sufficiently high ‘expression levels’ of HCN4 current the atrial cell is turned into a pacemaker cell with an SA nodal like action potential. Lower expression levels are sufficient if the inward rectifier potassium current (IK1), which is largely responsible for the stable resting potential of atrial cells, is ‘down-regulated’ by 50%, thus mimicking the gene therapy strategy to create a bio-pacemaker by down-regulation of IK1 and (over-)expression of If. Our dAPC experiments provide direct insights into the effects of introducing HCN4 current into an atrial cell, illustrating that dynamic action potential clamp can be a powerful tool in the process of developing a gene-based bio-pacemaker.

Published in:

Engineering in Medicine and Biology Society, 2008. EMBS 2008. 30th Annual International Conference of the IEEE

Date of Conference:

20-25 Aug. 2008

Need Help?


IEEE Advancing Technology for Humanity About IEEE Xplore | Contact | Help | Terms of Use | Nondiscrimination Policy | Site Map | Privacy & Opting Out of Cookies

A not-for-profit organization, IEEE is the world's largest professional association for the advancement of technology.
© Copyright 2014 IEEE - All rights reserved. Use of this web site signifies your agreement to the terms and conditions.