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Reduction of calcium currents by Lambert-Eaton syndrome sera: motoneurons are preferentially affected, and L-type
1Department of Anatomy and Neurobiology, Colorado State University, Fort Collins 80523, USA.
Abstract:
Previous work has demonstrated that Lambert-Eaton syndrome (LES) antibodies reduce calcium currents in nonneuronal cells and neurons and reduce the amplitude of extracellularly recorded currents at mouse motor nerve terminals. We compared effects of LES sera on whole-cell currents of cultured nerve and muscle. LES sera more strongly reduced calcium currents in motoneurons than in sensory neurons. Motoneuronal potassium currents were unaffected. The sera minimally affected calcium currents in skeletal and cardiac muscle. In motoneurons, both low voltage-activated (LVA) and high voltage-activated (HVA) components of calcium current were decreased, demonstrating that the sera targeted more than one calcium channel type. The HVA current remaining in LES-treated motoneurons was little affected by micromolar omega-conotoxin MVIIC but was reduced > 70% by micromolar nimodipine. This pharmacological profile contrasts with untreated cells and suggest that LES sera primarily spare L-type currents in motoneurons.
Insights
Lambert-Eaton syndrome (LES) antibodies impair calcium currents in nerve cells. LES sera primarily affect L-type calcium channels in motoneurons, sparing other channel types.
Area of Science:
- Neuroscience
- Immunology
- Cellular Physiology
Background:
- Lambert-Eaton syndrome (LES) is an autoimmune disorder affecting neuromuscular transmission.
- LES antibodies are known to reduce calcium currents in neurons and at motor nerve terminals.
- Previous studies indicate a broad impact of LES antibodies on neuronal calcium currents.
Purpose of the Study:
- To compare the effects of LES sera on whole-cell currents in cultured neurons and muscle cells.
- To determine the specific types of calcium channels affected by LES antibodies in motoneurons.
- To investigate the pharmacological profile of residual high-voltage-activated (HVA) calcium currents in LES-treated motoneurons.
Main Methods:
- Cultured rat motoneurons and sensory neurons were treated with LES sera.
- Whole-cell patch-clamp electrophysiology was used to measure calcium currents.
- Pharmacological agents, including omega-conotoxin MVIIC and nimodipine, were used to characterize HVA currents.
Main Results:
- LES sera significantly reduced calcium currents in motoneurons compared to sensory neurons.
- Both low-voltage-activated (LVA) and HVA calcium currents were decreased in motoneurons.
- Residual HVA currents in LES-treated motoneurons were largely insensitive to omega-conotoxin MVIIC but sensitive to nimodipine, suggesting a primary effect on L-type calcium channels.
Conclusions:
- LES antibodies exhibit differential effects on neuronal calcium currents, with a stronger impact on motoneurons.
- The sera target multiple calcium channel types, including both LVA and HVA components.
- LES antibodies appear to primarily spare L-type calcium channels in motoneurons, despite affecting other calcium channel subtypes.