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 present study characterizes the effects of A beta 31-35, a short active fragment of amyloid beta-peptide (A beta), upon the BK channel-mediated K. current and intracellular free Ca+ 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 ATPgated K+ channel blockers application of 5.0 mu M A beta 31-35 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 mu M but significantly increased by 12.5 mu M and 251.1.M A beta 31-35; and (3) when 25 1ih4 of a larger fragment of the amyloid 0-peptide, A beta 25-35, was applied, the results were similar to those obtained with the same concentration of A beta 31-35. These results indicate that A beta 31-35 is likely to be the shortest active fragment of the full A beta sequence, and can be as effectively as the fulllength Ap peptide in suppressing BK-channel mediated K+ currents and significantly elevating [Ca2+](i) in hippocampal CA1 neurons. (C) 2014 Elsevier Ireland Ltd. All rights reserved.