title: Effects of amyloid β-peptide fragment 31-35 on the BK channel-mediated K⁺ current and intracellular free Ca²⁺ concentration of hippocampal CA1 neurons.
abstract: 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 45mV; (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.
authors.affiliation: Department of Neurobiology, Shanxi Key Laboratory of Cell Physiology, Shanxi Medical University, Taiyuan, Shanxi 030001, PR China. Electronic address: zhyucnm@gmail.com.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Neurobiology, Shanxi Key Laboratory of Cell Physiology, Shanxi Medical University, Taiyuan, Shanxi 030001, PR China.
authors.forename: Zhi-Gang
authors.initials: ZG
authors.lastname: Shi
authors.affiliation: Department of Pathology, Shanxi Medical University, Taiyuan, Shanxi 030001, PR China.
authors.forename: Zhi-Hua
authors.initials: ZH
authors.lastname: Wang
authors.affiliation: Department of Neurobiology, Shanxi Key Laboratory of Cell Physiology, Shanxi Medical University, Taiyuan, Shanxi 030001, PR China.
authors.forename: Jian-Guo
authors.initials: JG
authors.lastname: Li
authors.affiliation: Functional Laboratory, Shanxi Medical University, Taiyuan, Shanxi 030001, PR China.
authors.forename: Jin-Yuan
authors.initials: JY
authors.lastname: Chen
authors.affiliation: Department of Neurobiology, Shanxi Key Laboratory of Cell Physiology, Shanxi Medical University, Taiyuan, Shanxi 030001, PR China. Electronic address: cezh2002@yahoo.com.
authors.forename: Ce
authors.initials: C
authors.lastname: Zhang
mesh_terms: D016229:Amyloid beta-Peptides / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D056547:CA1 Region, Hippocampal / Q000166:cytology / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D005260:Female; D042541:Intracellular Space / Q000378:metabolism; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000378:metabolism*; D008297:Male; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D018408:Patch-Clamp Techniques; D010446:Peptide Fragments / Q000378:metabolism / Q000494:pharmacology*; D011188:Potassium / Q000502:physiology*; D017207:Rats, Sprague-Dawley
chemical_list: D016229:Amyloid beta-Peptides; D051036:Large-Conductance Calcium-Activated Potassium Channels; D010446:Peptide Fragments; C113042:amyloid beta-protein (31-35); D011188:Potassium; D002118:Calcium
keywords: Aβ31–35; Ca(2+) imaging; Ca(2+)-activated big K(+) currents (BK currents); Hippocampal CAl neurons; Rats; Whole-cell patch recording