Amyloid β‐protein fragment 31–35 suppresses delayed rectifying potassium channels in membrane patches excised from hippocampal neurons in rats

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Abstract
To clarify the early initial mechanism underlying the neurotoxicity of amyloid β‐protein (AβP) and the shorter essential active sequence in native AβP molecules, the effects of AβP31–35 and AβP25–35 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 AβP31–35 (5 μM) 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 AβP25–35 at the same concentration showed similar effects as did the AβP31–35 application. It has generally been accepted that AβP25–35 acts as a full‐length AβP molecule does, so our findings suggest that the neurotoxicity of AβP may be initiated by the functional suppression of Ik channels and the sequence of 31–35 might be the shorter active sequence in AβP responsible for its neurotoxicity. Synapse 51:165–172, 2004.