Effects Of ATP-sensitive Potassium Channels Opener Iptakalim On Glutamate-induced Cytotoxicity In PC12 Cells

Glutamate, an excitatory neurotransmitter, is the most abundant neurotransmitter in the mammalian central nervous system (CNS), exerting essential physiological functions. However, overstimulation of the glutamatergic system promotes excitotoxicity and is implicated in the pathology of most neuron/glia death. Lucas and Newhouse firstly reported the damage of neuron exposed to glutamate extensively in 1957. The glutamate excitotoxicity means that the accumulation of glutamate in synaptic cleft by the excessive release or inhibited uptake of glutamate leads to the overactivation of NMDA receptors, which results in the intracellular calcium overload and finally the damage or apoptosis of neurons. Inhibiting glutmate release presynaptically or blocking its receptors' pathways underlying glutamate induced excitotoxicity postsynaptically may be neuroprotective in treating kinds of CNS disease.ATP-sensitive potassium channels (K_ATP), which link cell metabolism to its membrane potential, belong to a class of inwardly rectifying potassium channels that are activated by a decrease in the ATP/ADP ratio. Previous results including from our laboratory strongly indicated that activation of K_ATP might play an improtant role in protecting neurons against acute ischemia/hypoxia, oxidant or metabolic stress. Iptakalim hydrochloride (IPT), a lipophilic para-amino compound with low molecular weight, has been demonstrated to be a novel K_ATP opener (KCO) by extensive pharmacological,...