TY - JOUR
T1 - Selective disruption of neurotransmission by acetylcholinesterase antibodies in sympathetic ganglia examined with intracellular microelectrodes
AU - Miller, Steven M.
AU - Ermilov, Leonid G.
AU - Szurszewski, Joseph H.
AU - Hammond, Pamela I.
AU - Brimijoin, Stephen
N1 - Funding Information:
This work was supported by an NIH program project grant on Autonomic Disorders (NS32352) and by grant DK 17632 to J.H.S.
PY - 1997/12/11
Y1 - 1997/12/11
N2 - Antibodies to acetylcholinesterase (AChE) induce adrenergic dysfunction in rats by selective, complement-mediated destruction of preganglionic sympathetic nerve terminals. To analyze this phenomenon at the neuronal level, monoclonal antibodies to AChE (1.6 mg) were injected via the tail vein, and superior cervical ganglia (SCG) or inferior mesenteric ganglia (IMG) were studied in vitro. In control SCG, all impaled neurons generated action potentials during direct injection of depolarizing current or indirect stimulation through the preganglionic nerve. Current injection remained effective in ganglia from treated rats, but preganglionic stimulation was greatly impaired: at 12 h and 3 d, less than 10% of the neurons responded, even to a maximal stimulus (150 V); at 9 d, only 25% responded. By contrast, in IMG, synaptic transmission was much less affected by antibody exposure: 60% or more of examined neurons responded to preganglionic stimulation. Differences in antibody access did not explain differing sensitivities of SCG and IMG since immunohistochemistry showed rapid accumulation of IgG deposits in both ganglia. These results are believed to reflect widespread but subtotal preganglionic sympathectomy by AChE antibodies. Current information indicates that paravertebral ganglia are all antibody-sensitive, but some pre vertebral ganglia are resistant, suggesting immunochemical differences between them.
AB - Antibodies to acetylcholinesterase (AChE) induce adrenergic dysfunction in rats by selective, complement-mediated destruction of preganglionic sympathetic nerve terminals. To analyze this phenomenon at the neuronal level, monoclonal antibodies to AChE (1.6 mg) were injected via the tail vein, and superior cervical ganglia (SCG) or inferior mesenteric ganglia (IMG) were studied in vitro. In control SCG, all impaled neurons generated action potentials during direct injection of depolarizing current or indirect stimulation through the preganglionic nerve. Current injection remained effective in ganglia from treated rats, but preganglionic stimulation was greatly impaired: at 12 h and 3 d, less than 10% of the neurons responded, even to a maximal stimulus (150 V); at 9 d, only 25% responded. By contrast, in IMG, synaptic transmission was much less affected by antibody exposure: 60% or more of examined neurons responded to preganglionic stimulation. Differences in antibody access did not explain differing sensitivities of SCG and IMG since immunohistochemistry showed rapid accumulation of IgG deposits in both ganglia. These results are believed to reflect widespread but subtotal preganglionic sympathectomy by AChE antibodies. Current information indicates that paravertebral ganglia are all antibody-sensitive, but some pre vertebral ganglia are resistant, suggesting immunochemical differences between them.
KW - Adrenergic dysfunction
KW - Blood-ganglion barrier
KW - Colonofugal nerves
KW - Complement-mediated neural lesion
KW - Dysautonomia
KW - Inferior mesenteric ganglion
KW - Preganglionic neurons
KW - Superior cervical ganglion
KW - Sypnaptophysin
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U2 - 10.1016/S0165-1838(97)00119-7
DO - 10.1016/S0165-1838(97)00119-7
M3 - Article
C2 - 9479667
AN - SCOPUS:0031565160
SN - 0165-1838
VL - 67
SP - 156
EP - 167
JO - Journal of the Autonomic Nervous System
JF - Journal of the Autonomic Nervous System
IS - 3
ER -