Amyloid beta proteins reduce the GABA-induced Cl- current in identified Aplysia neurons.
The amyloid beta protein (A beta P) is the major component of the amyloid deposition which characterizes Alzheimer's disease. Effects of extracellularly applied A beta P on the gamma-aminobutyric acid (GABA)-induced Cl- current recorded from identified neurons (R9 and R12) of Aplysia kurodai were investigated with conventional voltage-clamp and pressure ejection techniques. Focal application of 100 nM A beta P (1-40) reduced the GABA-induced hyperpolarization at resting membrane potential and the GABA-induced Cl- current in the neurons held at -50 mV. Bath-applied 100 nM A beta P fragments (1-40) and (25-35) but not A beta P (1-16) inhibited the GABA-induced Cl- current as well as muscimol-induced Cl- currents in the neurons without affecting the resting membrane conductance or holding current. These results suggest that A beta P may increase neuronal excitability by inhibiting GABA-induced Cl- current in the neurons of mammalian central nervous system.
Sawada
M
M
Department of Physiology, Shimane Medical University, Izumo, Japan.
Ichinose
M
M
D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D000818:Animals; D001048:Aplysia; D018118:Chloride Channels / Q000187:drug effects*; D002712:Chlorides / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D018756:GABA Antagonists / Q000494:pharmacology; D017952:Ganglia, Invertebrate / Q000166:cytology / Q000187:drug effects; D008564:Membrane Potentials / Q000187:drug effects; D008845:Microinjections; D009433:Neural Inhibition / Q000187:drug effects; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D013997:Time Factors; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
D016229:Amyloid beta-Peptides; D018118:Chloride Channels; D002712:Chlorides; D018756:GABA Antagonists; D005680:gamma-Aminobutyric Acid