J Biol Chem 2021 Jan 16:100302. Epub 2021 Jan 16.
Department of Neuroscience, Center for Neuroscience, University of Pittsburgh, Pittsburgh, PA 15260, USA. Electronic address:
3,4-diaminopyridine (3,4-DAP) increases transmitter release from neuromuscular junctions (NMJs), and low doses of 3,4-DAP (estimated to reach ∼1 μM in serum) are the FDA-approved treatment for neuromuscular weakness caused by Lambert-Eaton Myasthenic Syndrome (LEMS). Canonically, 3,4-DAP is thought to block voltage-gated potassium (Kv) channels, resulting in prolongation of the presynaptic action potential (AP). However, recent reports have shown that low millimolar concentrations of 3,4-DAP have an off-target agonist effect on the Cav1 subtype ("L-type") of voltage-gated calcium (Cav) channels, and have speculated that this agonist effect might contribute to 3,4-DAP effects on transmitter release at the NMJ. Read More