Complex molecular mechanism for dihydropyridine binding to L-type Ca2+-channels as revealed by fluorescence resonance energy transfer

Examination of the binding-stimulated fluorescence properties of a fluorescent 1,4-dihydropyridine (DHP) and its analogue DMBODIPY-DHP helps investigate the molecular mechanism of the interaction of DHPs with alpha1-subunit of skeletal muscle L-type Ca2+-channels. Fluorescence yield of DMBODIPY-DHP decreases to specific binding. Binding permits the fluorescence resonance energy transfer (FRET) from between ligand and tryptophan residues to the alpha1-subunit. FRET signal helps direct measurements of DHP binding of high resolution. Application of this technique reveals a step-wise mechanism associated with reversible DHP binding to L-type Ca2+ channels.