Bis(3)-Tacrine Inhibits the Sustained Potassium Current in Cultured Rat Hippocampal Neurons

Abstract

Bis(3)-tacrine is a dimeric AChE inhibitor derived from tacrine with a potential to treat Alzheimer’s disease. It was recently been reported to act as a fast off-rate antagonist of NMDA receptors with moderate affinity. In the present study, we aimed to explore whether bis(3)-tacrine could modulate the function of native sustained potassium current in cultured rat hippocampal neurons using whole-cell patch-clamp technique. We found that bis(3)-tacrine inhibited the amplitude of sustained potassium current in a reversible and concentration-dependent manner, with a potency two orders of magnitude higher than that of tacrine. The inhibition was voltage-independent between 0 to +60 mV. The IC50 values for bis(3)-tacrine and tacrine inhibition of sustained potassium current were 0.450.07 and 50.54.8 μM, respectively. I-V curves showed a more potent inhibition of sustained potassium current by bis(3)-tacrine (1 μM) compared to tacrine at the same concentration. Bis(3)-tacrine hyperpolarized the activation curve of the current by 11.2 mV, albeit leaving the steady-state inactivation of the current unaffected.

Excavatolide-B Enhances Contextual Memory Retrieval via Repressing the Delayed Rectifier Potassium Current in the Hippocampus

“…Potassium current upregulation is involved in the Aβ peptide-induced apoptotic pathway and results in neuronal death [ 38 , 39 ]. Currently, the drugs for treating AD, including galantamine and bis (3)-tacrine, are acetylcholinesterase inhibitors with the ability to suppress the delayed rectifier potassium current [ 40 , 41 ]. The common side effects of galantamine are gastrointestinal symptoms, such as nausea, vomiting, diarrhea, and anorexia [ 42 ].…”