The standard treatment for bradycardic arrhythmias is the implantation of electronic pacemakers which have limitations regarding battery durability, lead failures or infections. An alternative could be an optical pacemaker and we have reported before, that light-induced pacing is technically feasible using transgenic mice that express the light-gated cation channel Channelrhodopsin-2 (ChR2).

Aim of the current study was to prove that light-induced pacing is possible in non-transgenic mice after gene transfer of ChR2 to the heart. We therefore injected adeno-associated viruses (AAV) of the serotype 2/1 (10 µl, 2 × 10¹¹ AAV particles) expressing ChR2 (H134R) in fusion with mCherry under the control of the chicken β-actin promoter into the myocardial wall of the left ventricle of 10 week old female CD1 wild-type mice. One week later, we could detect strong expression of mCherry in the vicinity of the injection site and histological sections showed mCherry fluorescence in the cell membrane and T-tubuli of cardiomyocytes. Optical pacing was applied in anesthetized and ventilated mice using an LED (470 nm) focussed through the open chest onto a circular region of 10.2 mm² of the left ventricle. Light pulses of various durations were applied at a frequency of ~ 40 bpm above the spontaneous beating rate and parallel ECG recording was used to analyze, if each light pulse induced ventricular pacing. We found that 1.82 ± 0.64 mW / mm² was sufficient for 2 ms (n = 7) and 0.95 ± 0.55 mW / mm² (n = 13) for 50 ms long light pulses to induce stable ventricular pacing.

Hence, AAV vectors can be used for gene transfer of ChR2 to the native myocardium and enable optical pacing of non-transgenic animals. Unfortunately, three weeks after AAV injection, optical pacing failed because the left ventricle developed fibrotic infarcts indicating a potential toxic or immunogenic effect of the AAV. Further experiments with lower dosages of AAV, systemic injection of AAV or immune-suppression are currently performed to explore the potential long term usage of this technique.