The Journal of Neuroscience, March 8, 2006, ():
Calcium Signaling Pathways Mediating Synaptic Potentiation Triggered by Amyotrophic Lateral Sclerosis IgG in Motor Nerve Terminals
J. Neurosci. Pagani et al.
26: 2661
Supplemental data
Files in this Data Supplement:
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Fig. S1. Hypothetical mechanism by which ALS-IgG may induce synaptic potentiation at MNT. We assumed that ALS-IgG-sp requires extracellular Ca2+ influx, but also that ALS-IgGs stimulate PLC (i.e., through G-protein coupled receptors or tyrosine kinase receptors), and generate IP3 (Fig. 6, 7 and 8). We excluded PLCδ activation and its participation since several pieces of evidence indicated that ALS-IgGs do not interact with Cav2.2 and that ALS-IgG-sp became independent of Ca2+ influx. In addition, Ca2+ influx through Cav2.2 channels induced by high K+ concentration, do not activate PLC since P/Q- type VDCC blocker removes the effect of high K+ concentration (see text). Thus, with low open probability there is likelihood for Cav2.2 channels to allow Ca2+ influx (1º), which may participate in the activation of individuals RyR and IP3R. The ALS-IgG contact with their unknown molecular target (1º) and activate PLC (2º), with the subsequent generation of IP3 (3º). Synergistic interaction of Ca2+ signal from Cav2.2 channels and IP3, activates IP3R and Ca2+ is released from intracellular Ca2+ stores. These elementary events can excite neighboring receptors through a process of CICR, to set up an intracellular Ca2+ mobilization (4º). Continuous and simultaneous Ca2+ release from RyR and IP3R (Fig.1C and 7B) may break down the equilibrium from a transient intracellular Ca2+ mobilization to a persistent Ca2+ mobilization (Berridge et al 2003), which would allow ALS-IgG-sp (5º).
