Mechanisms of dihydropyridine agonists and antagonists in view of cryo-EM structures of calcium and sodium channels

Opposite effects of 1,4-dihydropyridine (DHP) agonists and antagonists on the L-type calcium channels are a challenging problem. Cryo-EM structures visualized DHPs between the pore-lining helices S6III and S6IV in agreement with published mutational data. However, the channel conformations in the presence of DHP agonists and antagonists are virtually the same, and the mechanisms of the ligands' action remain unclear. We docked the DHP agonist …