PMID- 8538744
OWN - NLM
STAT- MEDLINE
DCOM- 19960208
LR  - 20181130
IS  - 0028-0836 (Print)
IS  - 0028-0836 (Linking)
VI  - 379
IP  - 6560
DP  - 1996 Jan 4
TI  - Activation of K+ channels and suppression of neuronal activity by secreted 
      beta-amyloid-precursor protein.
PG  - 74-8
AB  - The Alzheimer's beta-amyloid precursor protein (beta-APP) is widely expressed in 
      neural cells, and in neurons secreted forms of beta-APP (sAPPs) are released from 
      membrane-spanning holo-beta APP in an activity-dependent manner. Secreted APPs 
      can modulate neurite outgrowth, synaptogenesis, synaptic plasticity and cell 
      survival; a signal transduction mechanism of sAPPs may involve modulation of 
      intracellular calcium levels ([Ca2+]i). Here we use whole-cell perforated patch 
      and single-channel patch-clamp analysis of hippocampal neurons to demonstrate 
      that sAPPs suppress action potentials and hyperpolarize neurons by activating 
      high-conductance, charybdotoxin-sensitive K+ channels. Activation of K+ channels 
      by sAPPs was mimicked by a cyclic GMP analogue and sodium nitroprusside and 
      blocked by an antagonist of cGMP-dependent kinase and a phosphatase inhibitor, 
      suggesting that the effect is mediated by cGMP and protein dephosphorylation. 
      Calcium imaging studies indicate that activation of K+ channels mediates the 
      ability of sAPPs to decrease [Ca2+]i. Modulation of neuronal excitability may be 
      a major mechanism by which beta-APP regulates developmental and synaptic 
      plasticity in the nervous system.
FAU - Furukawa, K
AU  - Furukawa K
AD  - Sanders-Brown Research Center on Aging, University of Kentucky, Lexington 40536, 
      USA.
FAU - Barger, S W
AU  - Barger SW
FAU - Blalock, E M
AU  - Blalock EM
FAU - Mattson, M P
AU  - Mattson MP
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - Nature
JT  - Nature
JID - 0410462
RN  - 0 (Amyloid beta-Protein Precursor)
RN  - 0 (Ethers, Cyclic)
RN  - 0 (Potassium Channels)
RN  - 139890-68-9 (1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid 
      acetoxymethyl ester)
RN  - 169D1260KM (Nitroprusside)
RN  - 1W21G5Q4N2 (Okadaic Acid)
RN  - 526U7A2651 (Egtazic Acid)
RN  - H2D2X058MU (Cyclic GMP)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Action Potentials
MH  - Amyloid beta-Protein Precursor/metabolism/*physiology
MH  - Animals
MH  - Calcium/metabolism
MH  - Cell Line
MH  - Cells, Cultured
MH  - Cyclic GMP/analogs & derivatives/metabolism
MH  - Egtazic Acid/analogs & derivatives/pharmacology
MH  - Ethers, Cyclic/pharmacology
MH  - Hippocampus/cytology
MH  - Neural Inhibition
MH  - Neurons/*physiology
MH  - Nitroprusside/pharmacology
MH  - Okadaic Acid
MH  - Potassium Channels/drug effects/*metabolism
MH  - Rats
EDAT- 1996/01/04 00:00
MHDA- 1996/01/04 00:01
CRDT- 1996/01/04 00:00
PHST- 1996/01/04 00:00 [pubmed]
PHST- 1996/01/04 00:01 [medline]
PHST- 1996/01/04 00:00 [entrez]
AID - 10.1038/379074a0 [doi]
PST - ppublish
SO  - Nature. 1996 Jan 4;379(6560):74-8. doi: 10.1038/379074a0.