Cav2.1 voltage-dependent Ca2+ channel current is inhibited by serum from select patients with Guillain-Barré syndrome.
To investigate the pathophysiological mechanisms of immune-mediated peripheral neuropathies, we studied the effects of sera from patients with Guillain-Barré syndrome (GBS) on the Cav2.1 voltage-dependent calcium channel (VDCC) current in Purkinje cells. Using the whole-cell recording technique, Cav2.1 VDCC current was measured in cerebellar Purkinje cells in the presence of serum from GBS patients with acute motor axonal neuropathy (AMAN) or acute inflammatory demyelinating polyneuropathy (AIDP). The AMAN patient sera significantly inhibited the Cav2.1 VDCC current compared with healthy volunteer sera, and this inhibition was fully reversible by washing out the AMAN serum. Similarly, IgG purified from AMAN sera also inhibited the Cav2.1 VDCC current. However, the activation and inactivation kinetics of the Cav2.1 VDCC currents were not affected by serum from an AMAN patient. Moreover, the VDCC current of Purkinje cells was also inhibited by IgG anti-GM1 monoclonal antibody (anti-GM1 mAb). In an immunocytochemical study using double fluorescence staining, Purkinje cells were stained by monoclonal IgG anti-GM1 mAb. In contrast, AIDP patient and healthy volunteer sera did not affect the Cav2.1 VDCC current. These results suggest that in some case of GBS, particularly of AMAN patients with IgG anti-GM1 mAb, muscle weakness may be induced by dysfunction of Cav2.1 VDCC functioning at the motor nerve terminals.
Nakatani
Yoshihiko
Y
Departments of Pharmacotherapeutics, Showa Pharmaceutical University, Machida, Tokyo, 194-8543, Japan.
Hotta
Sayako
S
Utsunomiya
Iku
I
Tanaka
Keiko
K
Hoshi
Keiko
K
Ariga
Toshi
T
Yu
Robert K
RK
Miyatake
Tadashi
T
Taguchi
Kyoji
K
D000328:Adult; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D020864:Calcium Channels, N-Type / Q000187:drug effects / Q000502:physiology*; D005260:Female; D020275:Guillain-Barre Syndrome / Q000097:blood* / Q000503:physiopathology; D006801:Humans; D007074:Immunoglobulin G / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D010523:Peripheral Nervous System Diseases / Q000503:physiopathology; D011129:Polyradiculoneuropathy / Q000276:immunology; D020277:Polyradiculoneuropathy, Chronic Inflammatory Demyelinating / Q000503:physiopathology; D011689:Purkinje Cells / Q000187:drug effects / Q000502:physiology
D015220:Calcium Channels; D020864:Calcium Channels, N-Type; D007074:Immunoglobulin G