Effects of amyloid β-peptide fragment 31–35 on the BK channel-mediated K+ current and intracellular free Ca2+ concentration of hippocampal CA1 neurons

• The early-transient currents are from large conductance Ca2+-activated K+ channels.
• Aβ31–35 is the shortest active fragment of full Aβ sequence.
• Aβ31–35 could suppress the early-transient part of BK currents.
• Aβ31–35 elevated the intracellular load of Ca2+, as is the larger fragment Aβ25–35.

The present study characterizes the effects of Aβ31–35, a short active fragment of amyloid β-peptide (Aβ), upon the BK channel-mediated K+ current and intracellular free Ca2+ concentration ([Ca2+]i) of freshly dissociated pyramidal cells from rat CA1 hippocampus by using whole-cell patch-clamp recording and single cell Ca2+ imaging techniques. The results show that: (1) in the presence of voltage- and ATP-gated K+ channel blockers application of 5.0 μM Aβ31–35 significantly diminished transient outward K+ current amplitudes at clamped voltages between 0 and 45 mV; (2) under the same conditions [Ca2+]i was minimally affected by 5.0 μM but significantly increased by 12.5 μM and 25 μM Aβ31–35; and (3) when 25 μM of a larger fragment of the amyloid β-peptide, Aβ25–35, was applied, the results were similar to those obtained with the same concentration of Aβ31–35. These results indicate that Aβ31–35 is likely to be the shortest active fragment of the full Aβ sequence, and can be as effectively as the full-length Aβ peptide in suppressing BK-channel mediated K+ currents and significantly elevating [Ca2+]i in hippocampal CA1 neurons.