We placed a bright, photostable rhodamine in the intracellular domain of the human Nav1.5 by having a living cell splice in a chemically synthesized 77-mer peptide via two orthogonal split inteins. The signal tracks inactivation rather than activation and two things binding at distant sites, the auxiliary protein iFGF12A at the C-terminus and lidocaine in the pore, allosterically tune the kinetics of the DIII–DIV linker movements. This one took patience: many oocytes, lots of peptide, and a lot of persistence – big thanks to Laurie and the whole team for keeping at it, and to Lundbeck Foundation and the EU’s Marie Skłodowska-Curie Actions for funding. LINK
