Experimental strategy. The purpose of our study was to elicit light-induced APs not by coexpression of wild type ChR2 with voltage-gated Na+ channels, but by coupling ChR2 either directly to Nav1.5 (ChR2-Nav1.5, Nav1.5-ChR2) or to the accessory β1 subunit (β1-ChR2, β1-ChR2-ChR2). The seven transmembrane regions of ChR2 (blue), the four large domains of voltage-gated Na+ channels (red), the β1 subunit (orange), and the membrane-spanning region of the human H+/K+ATPase (gray) are illustrated. In Nav1.5-ChR2, β1-ChR2, and β1-ChR2-ChR2, peptide [GGGS]3 was incorporated into all linker regions (symbolized by a black line). For detailed amino acid composition of the constructs, see Materials and methods.