Reduction of calcium currents by Lambert-Eaton syndrome sera: motoneurons are preferentially affected, and L-type currents are spared.
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.
García
K D
KD
Department of Anatomy and Neurobiology, Colorado State University, Fort Collins 80523, USA.
Beam
K G
KG
D000818:Animals; D001769:Blood; D002118:Calcium / Q000502:physiology*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D004553:Electric Conductivity; D015624:Lambert-Eaton Myasthenic Syndrome / Q000097:blood*; D051379:Mice; D009046:Motor Neurons / Q000187:drug effects / Q000502:physiology*; D018482:Muscle, Skeletal / Q000502:physiology; D009553:Nimodipine / Q000494:pharmacology; D010210:Papillary Muscles / Q000502:physiology; D010455:Peptides / Q000494:pharmacology; D011188:Potassium / Q000502:physiology; D012016:Reference Values; D020960:omega-Conotoxins
D002121:Calcium Channel Blockers; D010455:Peptides; D020960:omega-Conotoxins; C075851:omega-conotoxin-MVIIC; D009553:Nimodipine; D011188:Potassium; D002118:Calcium