Amyloid-ß Protein Precursor Regulates Electrophysiological Properties in the Hippocampus via Altered Kv1.4 Expression and Function in Mice.
J Alzheimers Dis
; 92(4): 1241-1256, 2023.
Article
em En
| MEDLINE
| ID: mdl-36872774
ABSTRACT
BACKGROUND:
Amyloid-ß protein precursor (AßPP) is enriched in neurons. However, the mechanism underlying AßPP regulation of neuronal activity is poorly understood. Potassium channels are critically involved in neuronal excitability. In hippocampus, A-type potassium channels are highly expressed and involved in determining neuronal spiking.OBJECTIVE:
We explored hippocampal local field potential (LFP) and spiking in the presence and absence of AßPP, and the potential involvement of an A-type potassium channel.METHODS:
We used in vivo extracellular recording and whole-cell patch-clamp recording to determine neuronal activity, current density of A-type potassium currents, and western blot to detect changes in related protein levels.RESULTS:
Abnormal LFP was observed in AßPP-/- mice, including reduced beta and gamma power, and increased epsilon and ripple power. The firing rate of glutamatergic neurons reduced significantly, in line with an increased action potential rheobase. Given that A-type potassium channels regulate neuronal firing, we measured the protein levels and function of two major A-type potassium channels and found that the post-transcriptional level of Kv1.4, but not Kv4.2, was significantly increased in the AßPP-/- mice. This resulted in a marked increase in the peak time of A-type transient outward potassium currents in both glutamatergic and gamma-aminobutyric acid-ergic (GABAergic) neurons. Furthermore, a mechanistic experiment using human embryonic kidney 293 (HEK293) cells revealed that the AßPP deficiency-induced increase in Kv1.4 may not involve protein-protein interaction between AßPP and Kv1.4.CONCLUSION:
This study suggests that AßPP modulates neuronal firing and oscillatory activity in the hippocampus, and Kv1.4 may be involved in mediating the modulation.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Canais de Potássio
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Precursor de Proteína beta-Amiloide
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Canal de Potássio Kv1.4
Limite:
Animals
/
Humans
Idioma:
En
Revista:
J Alzheimers Dis
Ano de publicação:
2023
Tipo de documento:
Article