The Changes Of Voltage-Activated Potassium Channels In Dementia Induced By Impairment Of The Central Cholinergic System Function In Rats

It is generally agreed that the central muscarinic cholinergic system plays an important role in learning and memory processes. Alzheimer's disease (AD), the most common cause of dementia, is a devastating illness characterized by cognitive deterioration as well as behavioral, affective, and psychotic disturbances. The learning and cognitive deficits observed in AD patients are hypothesized to be partly caused by the loss of cholinergic neurons in the basal forebrain. Indeed, acetylcholinesterase inhibitors, such as. tacrine, donepezil, rivastigmine and galantamine are the only FDA-approved drugs currently marketed in the United States for the symptomatic treatment of AD.Potassium (K~+) channels perform a modulatory function in excitable and non-excitable cells by regulating K~+ conductance. In the CNS, K~+ channels have different distribution; opening of neuronal K~+ channels generally acts to dampen neuronal excitability via pre- or post-synaptic mechanisms. By applying different K~+ modulators in various experimental models, it has been demonstrated that K~+ channels play a critical role in the mechanisms of learning and memory. Acetylcholine increases pyramidal neurons excitability in hippocampus and neocortex by reducing or blocking several potassium currents, suggesting that the ionic mechanisms of the cholinergic excitatory might have some relations to distinct subtypes of potassium channels. In addition, potassium channel...