Biological pacemakers based on I(f).
Biological pacemaking as a replacement for or adjunct to electronic pacemakers has been a subject of interest since the 1990s. In the following pages, we discuss the rational for and progress made using a hyperpolarization activated, cyclic nucleotide gated channel isoform to carry the I(f) pacemaker current in gene and cell therapy approaches. Both strategies have resulted in effective biological pacemaker function over a period of weeks in intact animals. Moreover, the use of adult human mesenchymal stem cells as a platform for carrying pacemaker genes has resulted in the formation of functional gap junctions with cardiac myocytes in situ leading to effective and persistent propagation of pacemaker current. The approaches described are encouraging, suggesting that biological pacemakers based on this strategy can be brought to clinical testing.
Rosen
Michael R
MR
Department of Pharmacology, Center for Molecular Therapeutics, College of Physicians and Surgeons of Columbia University, New York, NY 10032, USA. mrr1@columbia.edu
Brink
Peter R
PR
Cohen
Ira S
IS
Robinson
Richard B
RB
D001145:Arrhythmias, Cardiac / Q000378:metabolism / Q000628:therapy*; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D015640:Ion Channel Gating; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D032383:Myocytes, Cardiac / Q000378:metabolism; D015221:Potassium Channels / Q000235:genetics* / Q000378:metabolism; D012849:Sinoatrial Node / Q000502:physiology
D015221:Potassium Channels