Alteration and amelioration of ionic currents in motoneuron-derived cellsmodelling spinal and bulbar muscular atrophy (SBMA)

Spinal and bulbar muscular atrophy (SBMA) is a motor neuron disease caused by the ex-pansion of a polymorphic CAG repeat encoding a polyglutamine (polyQ) tract in the an-drogen receptor (AR) gene. To investigate neuronal alterations, we patch-clamped mousemotoneuron-derived MN-1 cells expressing normal and mutant (dihydrotestosterone, DHT,binded) AR. We observed a reduction of macroscopic current at depolarizing potentialsin 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 ther-apeutic targets.