Lambert-Eaton Antibodies Inhibit Ca2+ Currents But Paradoxically Increase Exocytosis during Stimulus Trains in Bovine Adrenal Chromaffin Cells

Lambert-Eaton myasthenic syndrome (LEMS) is an autoimmune disease that affects neurotransmitter release at peripheral synapses. LEMS antibodies inhibit Ca2+ currents in excitable cells, but it is not known whether there are additional effects on stimulus-secretion coupling. The effect of LEMS antibo...

Full description

Saved in:
Bibliographic Details
Published in:The Journal of neuroscience 1999-05, Vol.19 (9), p.3384-3395
Main Authors: Engisch, Kathrin L, Rich, Mark M, Cook, Noah, Nowycky, Martha C
Format: Article
Language:English
Subjects:
Adrenal Medulla - cytology
Adrenal Medulla - physiology
Adult
Aged
Animals
Autoantibodies - blood
Autoantibodies - pharmacology
Calcium Channels - physiology
Cattle
Cells, Cultured
Chromaffin Cells - cytology
Chromaffin Cells - physiology
Evoked Potentials
Exocytosis
Female
Humans
Immunoglobulin G - blood
Immunoglobulin G - pharmacology
Lambert-Eaton Myasthenic Syndrome - blood
Lambert-Eaton Myasthenic Syndrome - immunology
Male
Membrane Potentials - drug effects
Middle Aged
Neuromuscular Junction - immunology
Neuromuscular Junction - physiology
omega-Conotoxin GVIA
Peptides - pharmacology
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Lambert-Eaton myasthenic syndrome (LEMS) is an autoimmune disease that affects neurotransmitter release at peripheral synapses. LEMS antibodies inhibit Ca2+ currents in excitable cells, but it is not known whether there are additional effects on stimulus-secretion coupling. The effect of LEMS antibodies on Ca2+ currents and exocytosis was studied in bovine adrenal chromaffin cells using whole-cell voltage clamp in perforated-patch recordings. Purified LEMS IgGs from five patients inhibited N- and P/Q-type Ca2+ current components to different extents. The reduction in Ca2+ current resulted in smaller exocytotic responses to single depolarizing pulses, but the normal relationship between integrated Ca2+ entry and exocytosis (Enisch and Nowycky, 1996) was preserved. The hallmark of LEMS is a large potentiation of neuromuscular transmission after high-frequency stimulation. In chromaffin cells, stimulus trains can induce activity-dependent enhancement of the Ca2+-exocytosis relationship. Enhancement during trains occurs most frequently when pulses are brief and evoke very small amounts of Ca2+ entry (Engisch et al., 1997). LEMS antibody treatment increased the percentage of trains eliciting enhancement through two mechanisms: (1) by reducing Ca2+ entry and (2) through a Ca2+-independent effect on the process of enhancement. This leads to a paradoxical increase in the amount of exocytosis during stimulus trains, despite inhibition of Ca2+ currents.
ISSN:0270-6474
1529-2401
DOI:10.1523/JNEUROSCI.19-09-03384.1999