Effects of Aβ1‐42 on the current of KATP channels in cultured cholinergic neurons.
OBJECTIVE
This study mainly determined the effect of beta-amyloid peptides (Abeta(1-42)) on the ATP-sensitive potassium (K(ATP)) channels of the cultured cortical and hippocampal cholinergic neurons, and further confirmed the protective effect of Diazoxide,  which was the specific opener of K(ATP) channels, to the neurons.


METHODS
The primary rat cortical and hippocampal cholinergic neurons were cultured. Membrane currents were measured using whole-cell patch-clamp technique.


RESULTS
The data showed that the outward  current of neurons significantly decreased after using Abeta(1-42) (P<0·05), and that the outward current of decreased did not change after given Diazoxide again (P>0·05) compared with control. However, after being pretreated with Diazoxide  for 1 hour before using Abeta(1-42), this phenomenon did not exist; that is, the membrane current of the neurons did not change when we give Abeta(1-42) after pretreatment with Diazoxide (P>0·05).


CONCLUSIONS
It is concluded that  Abeta(1-42) inhibits the openings of the K(ATP) channels, while this inhibitory action can be removed by pretreatment with Diazoxide. It is indicated that the opening of K(ATP) channels may play a potential neuroprotective role in antineurotoxicity of Abeta(1-42),  and the application of Diazoxide in small dose may be helpful in the treatment of Abeta(1-42) neurotoxicity.
Department of Neurology, Provincial Hospital affiliated to Shandong University, Jinan, China.
Shuhui
S
Tan
Guozhao
G
Ma
Yanju
Y
Li
Jingxin
J
Li
Wei
W
Yao
Xiaoyan
X
Ren
Xin
X
Liu
Jianxin
J
Gao
D016229:Amyloid beta-Peptides / Q000502:physiology*; D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D059329:Cholinergic Neurons / Q000187:drug effects / Q000502:physiology*; D003981:Diazoxide / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D005260:Female; D054086:KATP Channels / Q000037:antagonists & inhibitors* / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology*; D010446:Peptide Fragments / Q000502:physiology*; D026902:Potassium Channel Blockers / Q000494:pharmacology; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar
D016229:Amyloid beta-Peptides; D054086:KATP Channels; D010446:Peptide Fragments; D026902:Potassium Channel Blockers; C075222:amyloid beta-protein (1-42); D003981:Diazoxide