Alteration and amelioration of ionic currents in motoneuron-derived cells modelling spinal and bulbar muscular atrophy (SBMA).
Jiménez Garduño A.M., Juárez-Hernández L.J., Polanco M.J., Tosatto L., Michelatti D., Arosio D., Basso M., Pennuto M., Musio C.
Spinal and bulbar muscular atrophy (SBMA) is a motor neuron disease caused by the expansion of a polymorphic CAG repeat encoding a polyglutamine (polyQ) tract in the androgen receptor (AR) gene. To investigate neuronal alterations, we patch-clamped mouse motoneuron-derived MN-1 cells expressing normal and mutant (dihydrotestosterone, DHT, binded) AR. We observed a reduction of macroscopic current at depolarizing potentials in DHT treated cells and single cationic currents were ascribed to voltage-gated channels. Treatment with IGF-1 and PACAP rescuers showed amelioration of the altered currents. We propose the ionic channel activity useful for identifiying the disease symptoms and therapeutic targets.