Electrotonic coupling of excitable and nonexcitable cells in the heart revealed by optogenetics

Heart pumping is triggered and coordinated by action potentials (APs) originating in and spreading among electrically excitable heart muscle cells (myocytes) via electrotonic coupling. Cardiac nonmyocytes are thought not to participate in AP conduction in situ, although heterocellular electrotonic coupling is common in cell culture. We used optogenetic tools involving cell-specific expression of a voltage-reporting fluorescent protein to monitor electrical activity in myocytes or nonmyocytes of mouse hearts. We confirm the suitability of this technique for measuring cell type-specific voltage signals and show that, when expressed in nonmyocytes, myocyte AP-like signals can be recorded in cryoinjured scar border tissue. This direct evidence of heterocellular electrotonic coupling in the whole heart necessitates a review of current concepts on cardiac electrical connectivity.