Amyloid beta-protein fragment 31-35 suppresses delayed rectifying potassium channels in membrane patches excised from hippocampal neurons in rats.
To clarify the early initial mechanism underlying the neurotoxicity of amyloid beta-protein (AbetaP) and the shorter essential active sequence in native AbetaP molecules, the effects of AbetaP31-35 and AbetaP25-35 on delayed rectifier K+ current (Ik) were investigated in the inside-out membrane patches excised from hippocampal neurons of rats. The results showed that: 1) After application of AbetaP31-35 (5 microM) to the inside of patches, the average open frequency and open probability of Ik channels reversibly decreased by 70.45 +/- 35.75% and 86.9 +/- 11.13%, respectively; the mean open time decreased by 47.1 +/- 38.8%, while the mean current amplitude of Ik channels was not significantly affected. 2) Application of AbetaP25-35 at the same concentration showed similar effects as did the AbetaP31-35 application. It has generally been accepted that AbetaP25-35 acts as a full-length AbetaP molecule does, so our findings suggest that the neurotoxicity of AbetaP may be initiated by the functional suppression of Ik channels and the sequence of 31-35 might be the shorter active sequence in AbetaP responsible for its neurotoxicity.
Qi
Jin-Shun
JS
Department of Neurobiology, Shanxi Medical University, Taiyuan, Shanxi 030001, PR China. jinshunqi@sohu.com
Ye
Lan
L
Qiao
Jian-Tian
JT
D015761:4-Aminopyridine / Q000494:pharmacology; D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn; D002118:Calcium / Q000494:pharmacology; D002586:Cesium / Q000494:pharmacology; D002712:Chlorides / Q000494:pharmacology; D051668:Delayed Rectifier Potassium Channels; D004553:Electric Conductivity; D006624:Hippocampus / Q000166:cytology*; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D018408:Patch-Clamp Techniques / Q000379:methods; D010446:Peptide Fragments / Q000494:pharmacology*; D011188:Potassium / Q000494:pharmacology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism*; D024642:Potassium Channels, Voltage-Gated; D051381:Rats; D017208:Rats, Wistar; D019789:Tetraethylammonium / Q000494:pharmacology; D013997:Time Factors
D016229:Amyloid beta-Peptides; D002712:Chlorides; D051668:Delayed Rectifier Potassium Channels; D010446:Peptide Fragments; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; C113042:amyloid beta-protein (31-35); D002586:Cesium; D019789:Tetraethylammonium; D015761:4-Aminopyridine; C028019:cesium chloride; D011188:Potassium; D002118:Calcium