Engineering a biological pacemaker: in vivo, in vitro and in silico models

Several hundred thousand electronic pacemakers are implanted in the US each year to treat abnormally slow heart rates. Biological pacemaker research strives to replace this hardware, and the associated monitoring and maintenance, by using gene or cell therapy to create a permanent and autonomically responsive pacemaker. While there are numerous technological hurdles to overcome before this is a therapeutic reality, one critical issue is determining the optimal channel gene to employ in creating a biological pacemaker. This review discusses the pros and cons of various model systems for characterizing and evaluating the function of candidate channel genes. It is argued that a sequential approach that combines in silico, in vitro and in vivo models is required.