Suppression of large conductance Ca2+-activated K+ channels by amyloid beta-protein fragment 31-35 in membrane patches excised from hippocampal neurons.
To clarify the shortest essential active sequence in amyloid beta-protein (AbetaP) responsible for affecting neuronal electrophysiological properties, the effects of fragments 31-35 and 25-35 of AbetaP on the large conductance Ca(2+)-activated potassium (BK) channels were investigated in the "inside-out" membrane patches excised from hippocampal neurons of rats. After application of AbetaP 3l-35 (5 micromol/L, n=10), the mean P(o) and open frequency of BK channels decreased by 85.8+/-l3.5 percent;percent; (P<0.01) and 72.1+/-22.8 percent; (P<0.01), respectively, and the mean open time decreased by 41.l+/-l8.5 percent; (P<0.0l), while the mean current amplitude was not significantly affected (P>0.05). Application of AbetaP 25-35 (5 micromol/L) also induced a decrease of 85.5+/-22.l percent; (P<0.0l) in mean P(o) and of 5l.4+/-18.3 percent; (P<0.05) in mean open time within l~3 min after application. These results suggest that the functional alteration in BK channels elicited by AbetaP fragments may play an important role in the mechanisms underlying AbetaP neurotoxicity, and AbetaP 31-35 may be the shortest active sequence in AbetaP responsible for affecting the electrophysiological properties of neurons.
Qi
J S
JS
Department of Neurobiology, Shanxi Medical University, Taiyuan 030001.
Qiao
J T
JT
D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000494:pharmacology; D002469:Cell Separation; D004594:Electrophysiology; D006624:Hippocampus / Q000166:cytology* / Q000502:physiology; D051036:Large-Conductance Calcium-Activated Potassium Channels; D009474:Neurons / Q000502:physiology; D018408:Patch-Clamp Techniques; D010446:Peptide Fragments / Q000494:pharmacology*; D026902:Potassium Channel Blockers / Q000494:pharmacology; D024681:Potassium Channels, Calcium-Activated / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D016229:Amyloid beta-Peptides; D051036:Large-Conductance Calcium-Activated Potassium Channels; D010446:Peptide Fragments; D026902:Potassium Channel Blockers; D024681:Potassium Channels, Calcium-Activated; C439320:amyloid beta-protein (25-36); C113042:amyloid beta-protein (31-35); D002118:Calcium