The physiological response during optogenetic-based cardiac pacing in awake freely moving mice

Jun Kaminosono; Yuki Kambe; Akihide Tanimoto; Tomoyuki Kuwaki; Akira Yamashita

doi:10.3389/fphys.2023.1130956

The physiological response during optogenetic-based cardiac pacing in awake freely moving mice

Front Physiol. 2023 Sep 6:14:1130956. doi: 10.3389/fphys.2023.1130956. eCollection 2023.

Authors

Jun Kaminosono¹, Yuki Kambe², Akihide Tanimoto³, Tomoyuki Kuwaki¹, Akira Yamashita^{1

4}

Affiliations

¹ Department of Physiology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.
² Department of Pharmacology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.
³ Department of Pathology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.
⁴ Department of Medical Neuropharmacology, Wakayama Medical University School of Pharmaceutical Sciences, Wakayama, Japan.

Abstract

There are several methods to control a heart rate, such as electrical stimulation and drug administration. However, these methods may be invasive or affect other organs. Recently, an optogenetic-based cardiac pacing method has enabled us to stimulate the cardiac muscle in non-contact. In many previous studies, the pacing was applied ex vivo or in anesthetized animals. Therefore, the physiologic response of animals during optogenetic pacing remains unclear. Here, we established a method of optogenetic-based cardiac pacing in awake, freely moving mice and simultaneously measured electrocardiogram, blood pressure, and respiration. As a result, light-induced myocardial contraction produces blood flow and indirectly affects the respiration rhythm. Additionally, light illumination enabled heart rate recovery in bradycardic mice. These findings may be employed for further research that relates a heartbeat state to animal behavior. Together, this method may drive the development of less invasive pacemakers without pacing leads.

Keywords: blood pressure; cardiac pacing; heart rate; optogenetics; pacemaker; respiration.

Grants and funding

This work was supported by the Japan Society for the Promotion of Science (JSPS) KAKENHI Grants (17K14936 and 20K06858 to AY, 20K07067 to YK, and 16H05130 to TK), a grant from the Miyata Cardiac Research Promotion Foundation to AY, The Yokoyama Foundation (Exploratory Research for Clinical Pharmacology to AY), and SENSHIN Medical Research Foundation (Circulation Research Grant for Young Scientists to AY).