The pathogenesis of the second major neurodegenerative disorder, Parkinson’s disease(PD), is closely associated with the dysfunction of potassium(K~+ ) channels. Therefore, PD is also considered to be an ion channel ...The pathogenesis of the second major neurodegenerative disorder, Parkinson’s disease(PD), is closely associated with the dysfunction of potassium(K~+ ) channels. Therefore, PD is also considered to be an ion channel disease or neuronal channelopathy. Mounting evidence has shown that K~+ channels play crucial roles in the regulations of neurotransmitter release, neuronal excitability, and cell volume. Inhibition of K~+ channels enhances the spontaneous firing frequency of nigral dopamine(DA)neurons, induces a transition from tonic firing to burst discharge, and promotes the release of DA in the striatum.Recently, three K~+ channels have been identified to protect DA neurons and to improve the motor and non-motor symptoms in PD animal models: small conductance(SK)channels, A-type K~+ channels, and KV7/KCNQ channels.In this review, we summarize the physiological and pharmacological effects of the three K~+ channels. We also describe in detail the laboratory investigations regarding K~+ channels as a potential therapeutic target for PD.展开更多
Trigeminal inflammatory pain is one of the most severe pain-related disorders in humans;however,the underlying mechanisms remain largely unknown.In this study,we investigated the possible contribution of interaction b...Trigeminal inflammatory pain is one of the most severe pain-related disorders in humans;however,the underlying mechanisms remain largely unknown.In this study,we investigated the possible contribution of interaction between ten-eleven translocation methylcytosine dioxygenase 1(TET1)and the voltage-gated K^(+)channel Kv7.2(encoded by Kcnq2)to orofacial inflammatory pain in mice.We found that complete Freund’s adjuvant(CFA)injection reduced the expression of Kcnq2/Kv7.2 in the trigeminal ganglion(TG)and induced orofacial inflammatory pain.The involvement of Kv7.2 in CFA-induced orofacial pain was further confirmed by Kv7.2 knockdown or overexpression.Moreover,TET1 knockdown in Tet1^(flox/flox)mice significantly reduced the expression of Kv7.2 and M currents in the TG and led to pain-like behaviors.Conversely,TET1 overexpression by lentivirus rescued the CFA-induced decreases of Kcnq2 and M currents and alleviated mechanical allodynia.Our data suggest that TET1 is implicated in CFA-induced trigeminal inflammatory pain by positively regulating Kv7.2 in TG neurons.展开更多
基金supported by the National Natural Science Foundation of China(31671054 and 81430024)the Postdoctoral Science Foundation of China(2017M610412)the Bureau of Science and Technology of Qingdao Municipality,China(17-1-1-44-jch)
文摘The pathogenesis of the second major neurodegenerative disorder, Parkinson’s disease(PD), is closely associated with the dysfunction of potassium(K~+ ) channels. Therefore, PD is also considered to be an ion channel disease or neuronal channelopathy. Mounting evidence has shown that K~+ channels play crucial roles in the regulations of neurotransmitter release, neuronal excitability, and cell volume. Inhibition of K~+ channels enhances the spontaneous firing frequency of nigral dopamine(DA)neurons, induces a transition from tonic firing to burst discharge, and promotes the release of DA in the striatum.Recently, three K~+ channels have been identified to protect DA neurons and to improve the motor and non-motor symptoms in PD animal models: small conductance(SK)channels, A-type K~+ channels, and KV7/KCNQ channels.In this review, we summarize the physiological and pharmacological effects of the three K~+ channels. We also describe in detail the laboratory investigations regarding K~+ channels as a potential therapeutic target for PD.
基金supported by the National Natural Science Foundation of China(81771195 and 81971061)the Program for Innovative Research Team in Universities of Henan Province(22IRTSTHN028).
文摘Trigeminal inflammatory pain is one of the most severe pain-related disorders in humans;however,the underlying mechanisms remain largely unknown.In this study,we investigated the possible contribution of interaction between ten-eleven translocation methylcytosine dioxygenase 1(TET1)and the voltage-gated K^(+)channel Kv7.2(encoded by Kcnq2)to orofacial inflammatory pain in mice.We found that complete Freund’s adjuvant(CFA)injection reduced the expression of Kcnq2/Kv7.2 in the trigeminal ganglion(TG)and induced orofacial inflammatory pain.The involvement of Kv7.2 in CFA-induced orofacial pain was further confirmed by Kv7.2 knockdown or overexpression.Moreover,TET1 knockdown in Tet1^(flox/flox)mice significantly reduced the expression of Kv7.2 and M currents in the TG and led to pain-like behaviors.Conversely,TET1 overexpression by lentivirus rescued the CFA-induced decreases of Kcnq2 and M currents and alleviated mechanical allodynia.Our data suggest that TET1 is implicated in CFA-induced trigeminal inflammatory pain by positively regulating Kv7.2 in TG neurons.
