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Neuropathic pain is a common chronic pain that affects human health worldwide. As an important mediator of excitatory conduction in neurons, ion channels are important targets for mechanism research and drug research in this field. T-type calcium channel(Cav3) can be activated transiently when neurons are close to the resting potential of -70 mV, resulting in a transient Ca
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ABSTRACT:Objective To investigate the mechanism and induction of T type calcium channel on neural stem cells after brain injury .Methods Adult mice brain injury model was established and divided into control ,sham operation ,surgery ,and surgery+mebefradil groups .Neural stem cells were separated from the subventricular zone (SVZ) and identified .Moreover ,we analyzed the results using MTT and neural stem cell sphere counting after adding different doses of mibefradil in culture medium ,respectively .Then we calculated the half maximal inhibitory concentration (IC50) of mibefradil on neural stem cells .Finally ,we analyzed the expression of Cav3 .2 in SVZ and the protein expressions of Cav3 .2 ,Cyclin A and caspase‐3 in neural stem cells by Western blot .Results In vivo , neural stem cell proliferation was increased in surgery group compared with that in control and sham‐operation groups .The proliferation of neural stem cells in surgery + mibefradil groups was significantly decreased compared with that in surgery group after mibefradil‐induced inhibition of T type calcium channel protein . In vitro , the formation of neural stem cell sphere was significantly inhibited after adding mibefradil .The cell growth ratio was significantly decreased when the concentration of mibefradil was above 5μmol/L .A values in 5 μmol/L ,10 μmol/L and 20μmol/L groups were significantly lower than those in control group (P<0 .05) .IC50 was 8 .93μmol/L .The protein expressions of Cyclin A and Cav3 .2 were inhibited while that of caspase‐3 was increased after mibefradil treatment .Conclusion Neural stem cell proliferation was enhanced by activating T type calcium channel after brain injury .
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T-type calcium channels are expressed in various tis-sues and play key roles in physiology and pathophysiology,inclu-ding neuronal firing,hormone secretion,pain,and cancer,etc. Hence,it is critical to understand the molecular mechanisms un-derlying the regulation of T-type channels.Substantial literature suggests many G protein-coupled receptors (GPCRs)and related second messengers can modulate T-type channel in some extent. Here,this review focuses on the modulation of T-type calcium channels by GPCRs and related second messengers.