IGG FROM AMYOTROPHIC-LATERAL-SCLEROSIS PATIENTS INCREASES CURRENT THROUGH P-TYPE CALCIUM CHANNELS IN MAMMALIAN CEREBELLAR PURKINJE-CELLS AND IN ISOLATED CHANNEL PROTEIN IN LIPID BILAYER

The effect of the IgG from amyotrophic lateral sclerosis (ALS) patient s was tested on the voltage-dependent barium currents (I(Ba)) in mamma lian dissociated Purkinje cells and in isolated P-type calcium channel s in lipid bilayers. Whole cell clamp of Purkinje cells demonstrates t hat ALS IgG increases the amplitude of I(Ba) without modifying their v oltage kinetics. This increased I(Ba) could be blocked by a purified n onpeptide toxin from Agelenopsis aperta venom (purified funnel-web spi der toxin) or by a synthetic polyamine analog (synthetic funnel-web sp ider toxin) and by a peptide toxin from the same spider venom, omega-A ga-IVA. Similar results were obtained on single-channel recordings fro m purified P channel protein. The addition of ALS IgG increased single -channel I(Ba) open time without affecting slope conductance. The resu lts described above were not seen with normal human IgG nor with boile d ALS IgG. It is concluded that ALS IgG enhances inward current throug h P-type calcium channels. Since P-type Ca2+ channels are present in m otoneuron axon terminals, we propose that the enhanced calcium current triggered by ALS IgG may contribute to neuronal damage in ALS.