AβP31–35 inhibits I A currents in hippocampal CA1 neurons in rats

Excessive extracellular depositions of amyloid β‐protein (AβP) in brain areas are the invariant characteristic features of Alzheimer's disease (AD). It has generally accepted that the shorter fragment of AβP, AβP25–35, possesses all the biological activities of full‐length AβP molecule, recent studies showed that AβP31–35, a shortest fragment of AβP, also possesses similar neurotoxicity. The present study was undertaken to observe effects of AβP31–35 on the fast‐inactivating K + (I A ) and delay‐rectifying K + (I K ) currents in rat hippocampal CA1 neurons using whole‐cell patch clamp technique; the effects of AβP25–35 were also observed, which could be as a positive control. After application of AβP31–35 (5 mmol/L) to bath solution, the average membrane conductance of I A channels decreased by 61.62±9.63% (n = 13, p<0.01), while the conductance of I K channels was not affected by the same concentration of AβP31–35 (n = 10, p>0.05). The kinetic analysis indicated that the steady‐state inactivation curve of I A channels was shifted to the left after application of AβP31–35, and the value of Vh (the potential of the half‐maximal activation) changed from −61.77±1.25 mV to −75.26±1.14 mV (n = 13, p<0.01), while the Vh in the activation curve of I A channels did not alter before and after application of AβP31–35 (n=13, p>0.05). Application of AβP25–35 exhibited similar effects as the AβP31–35 (n=10, p<0.01). The present results suggest that I A channels in hippocampal neurons might be involved in the effects of AβP, and AβP31–35 might be a shorter active sequence in AβP responsible for the neurotoxin of AβP in AD.