Development of a Genetically Engineered Cardiac Pacemaker: Insights from Dynamic Action Potential Clamp Experiments
In this chapter, we briefly review the use of dynamic clamp in cardiac cellular electrophysiology and present novel results obtained with the ‘dynamic action potential clamp’ (dAPC) technique. This is a technique that we recently developed to study the effects of long-QT syndrome-related ion channel mutations by effectively replacing the associated native ionic current of a cardiac myocyte with wild-type or mutant current recorded from a HEK-293 cell that is voltage clamped by the free-running action potential of the myocyte. Here we demonstrate that the dAPC technique can also be used as a powerful tool in the development of a ‘biological pacemaker’ or ‘bio-pacemaker,’ i.e. a genetically engineered cardiac pacemaker. We record ‘pacemaker current’ from an HCN4-transfected HEK-293 cell and inject this current into a model of a human atrial cell of which the free-running membrane potential is used to voltage clamp the HEK-293 cell. Thus we explore the conditions under which this HCN4-based pacemaker current turns the atrial cell into a pacemaker cell.
KeywordsAtrial Cell HERG Channel HCN4 Channel HERG Current Dynamic Clamp
We thank Berend de Jonge for expert biotechnical assistance.
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