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.

Abstract

The effect of the IgG from amyotrophic lateral sclerosis (ALS) patients was tested on the voltagedependent barium currents (IB.) Amyotrophic lateral sclerosis (ALS; "Lou Gehrig's disease") has been proposed to be an autoimmune disease that can attack upper and lower motoneurons (1), leading to paralysis, respiratory depression, and death. It has been previously reported that IgG from ALS patients has a blocking effect on L-type calcium channels (2) and in lipid bilayer (3). In addition, ALS IgG enhances calcium currents (Ica) in immortalized motoneurons (4), acting on an as yet unidentified calcium channel. This IgG has also been shown to produce an increase in acetylcholine release (5), a mechanism in which the P-type calcium channel is directly involved (6). Here, we demonstrate, using patch-clamp recordings from Purkinje cells (7,8), that ALS IgG produces an increase in barium current (IB.). A parallel experiment using purified P-type calcium channels isolated from the cerebellum and incorporated into a lipid bilayer (9,10)

Calcium Signaling Pathways Mediating Synaptic Potentiation Triggered by Amyotrophic Lateral Sclerosis IgG in Motor Nerve Terminals

“…reported in muscle fibers, granule cells, and dorsal root ganglion cells (Delbono et al, 1991;Zhainazarov et al, 1994;Yan et al, 1997), as well as an increase of currents in cell line VSC4.1 and Purkinje cells (Llinas et al, 1993;Mosier et al, 1995). Although patients with ALS may generate diverse antibodies against different types of VDCCs, those works did not support this hypothesis.…”

Single-Cell RT-PCR and Functional Characterization of Ca2+Channels in Motoneurons of the Rat Facial Nucleus

“…In addition, they are also expressed in the soma and dendrites, where they have been shown to be involved in the control of firing properties, both directly and through the activation of other Ca 2ϩ -dependent membrane conductances (Viana et al, 1993). Furthermore, Ca 2ϩ signaling, possibly involving Ca 2ϩ entry through voltage-gated Ca 2ϩ channels, has been implicated as a mechanism involved in the degeneration of motoneurons in amyotrophic lateral sclerosis (ALS) (Uchitel et al, 1988;Llinás et al, 1993;Mosier et al, 1995). Changes in Ca 2ϩ channel types involved in transmitter release at the endplate also accompany axon growth and muscle reinnervation after axotomy of adult motoneurons (Katz et al, 1996).…”

Differential Localization of Voltage-Dependent Calcium Channel α1Subunits at the Human and Rat Neuromuscular Junction

“…Several lines of evidence suggest that AL S autoantibodies may interact with V DCC s in MN terminals to affect calcium flux and M N f unction. First, ALS IgG has been shown to increase calcium flux through P-type channels (Llinás et al, 1993) and to stimulate the spontaneous release of acetylcholine at the mouse NMJ . Second, mice injected with AL S IgG exhibited an increase in synaptic vesicle number and intracellular calcium levels in MN terminals (Engelhardt et al, 1995).…”