Intravenous immunoglobulin preparation increases myoplasmic calcium concentration by activating the dihydropyridine-ryanodine receptor complex.
A human intravenous immunoglobulin preparation (IVIg) released Ca2+ from the sarcoplasmic reticulum of cultured human skeletal muscle cells in a dose-dependent manner. Blocking the dihydropyridine-ryanodine receptor complex abrogated the IVIg-mediated Ca2+ response, whereas inhibition of the voltage-operated Na+-channels or acetylcholine receptors did not. This effect of IVIg was not mediated by its main component, the IgG molecules, and differed between preparations from different manufacturers. Heating destroyed the activity. Data shows that an unidentified serum protein present in IVIg can influence human muscle cells by an effect on the dihydropyridine receptor. This phenomenon may be important in interpreting the (side) effects of IVIg in neuromuscular diseases.
van Engelen
B G
BG
Department of Neurology, University Hospital Nijmegen, The Netherlands. b.vanengelen@czzoneu.azn.nl
Benders
A A
AA
Wevers
R A
RA
Gabreëls
F J
FJ
Renier
W O
WO
Veerkamp
J H
JH
D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism*; D020746:Calcium Channels, L-Type; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000008:administration & dosage / Q000494:pharmacology*; D009124:Muscle Proteins / Q000378:metabolism; D011485:Protein Binding; D019837:Ryanodine Receptor Calcium Release Channel / Q000378:metabolism*; D012519:Sarcoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism
D015220:Calcium Channels; D020746:Calcium Channels, L-Type; D016756:Immunoglobulins, Intravenous; D009124:Muscle Proteins; D019837:Ryanodine Receptor Calcium Release Channel; D002118:Calcium