Generation of cardiac pacemaker cells by programming and differentiation

Publication date: Available online 8 December 2015 Source:Biochimica et Biophysica Acta (BBA) - Molecular Cell Research Author(s): Britta Husse, Wolfgang-Michael Franz A number of diseases is caused by faulty function of the cardiac pacemaker and described as “sick sinus syndrome”. The medical treatment of sick sinus syndrome with electrical pacemaker implants in the diseased heart includes risks. These problems may be overcome via “biological pacemaker” derived from different adult cardiac cells or pluripotent stem cells. The generation of cardiac pacemaker cells requires the understanding of the pacing automaticity. Two characteristic phenomena the “membrane-clock” and the “Ca2+-clock” are responsible for the modulation of the pacemaker activity. Processes in the “membrane-clock” generating the spontaneous pacemaker firing are based on the voltage-sensitive membrane ion channel activity starting with slow diastolic depolarization and discharging in the action potential. The influence of the intracellular Ca2+ modulating the pacemaker activity is characterized by the “Ca2+-clock”. The generation of pacemaker cells started with the reprogramming of adult cardiac cells by targeted induction of one pacemaker function like HCN1-4 overexpression and enclosed in an activation of single pacemaker specific transcription factors. Reprogramming of adult cardiac cells with the transcription factor Tbx18 created cardiac cells with characteristic features ...
Source: Biochimica et Biophysica Acta (BBA) Molecular Cell Research - Category: Molecular Biology Source Type: research