Amyloid β-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 P-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 (10 were investigated in the inside-out membrane patches excised from hippocampal neurons of rats. The results showed that: 1) After application of AXP31-35 (5 muM) to the inside of patches, the average open frequency and open probability Of I-k 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 I-k channels and the sequence of 31-35 might be the shorter active sequence in AbetaP responsible for its neurotoxicity. (C) 2003 Wiley-Liss, Inc.