Effects of Abeta1-42 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.