Abnormal changes in voltage-gated sodium channels NaV1.1, NaV1.2, NaV1.3, NaV1.6 and in calmodulin/calmodulin-dependent protein kinase II, within the brains of spontaneously epileptic rats and tremor rats

2013 ◽  
Vol 96 ◽  
pp. 1-9 ◽  
Author(s):  
Xiaoxue Xu ◽  
Feng Guo ◽  
Xintong Lv ◽  
Rui Feng ◽  
Dongyu Min ◽  
...  
Circulation ◽  
2012 ◽  
Vol 126 (17) ◽  
pp. 2084-2094 ◽  
Author(s):  
Olha M. Koval ◽  
Jedidiah S. Snyder ◽  
Roseanne M. Wolf ◽  
Ryan E. Pavlovicz ◽  
Patric Glynn ◽  
...  

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Chunhong Song ◽  
Jieqiong Wang ◽  
Dongmei Gao ◽  
Yanhong Yu ◽  
Fang Li ◽  
...  

The aim of this study was to explore the mechanism underlying the antidepression activity of paeoniflorin, the main active ingredient of paeony extract and Shuyu capsules, and determine its effect on the calmodulin/calmodulin-dependent protein kinase II (CaM/CaMKII) signalling pathway and on the possible target, the voltage-gated calcium channel (Cav). Rats at the nonacceptance stage were selected for premenstrual syndrome (PMS) depression modelling. Behavioural assays were used for model testing. Rats were given Shuyu capsules, paeony extract, and bupleurum. Western blot analysis was used to assess the expression levels of calcium voltage-gated channel subunit alpha 1 C (CACNA1C), brain-derived neurotrophic factor, and CaM/CaMKII signalling pathway proteins. Intracellular Ca2+ concentration in CHO cell line was measured using Fluo-4-AM and whole-cell patch clamps. The PMS depression model was successfully established and demonstrated that Shuyu can mitigate depressive behaviour in a rat PMS model. Paeony extract did not affect CACNA1C protein expression in rat hippocampi but did affect Cav1.2-mediated CaM/CaMKII signalling pathways. Paeoniflorin significantly inhibited KCl-induced increases in intracellular Ca2+ concentration and Cav1.2 current density. Further, it may function via the CaM/CaMKII pathway and its downstream signalling molecules by regulating Cav1.2, thus playing an important role in the treatment and alleviation of affective disorders.


2019 ◽  
Vol 17 (3) ◽  
pp. 249-253
Author(s):  
Liu Chenglong ◽  
Liu Haihua ◽  
Zhang Fei ◽  
Zheng Jie ◽  
Wei Fang

Cancer-induced bone pain is a severe and complex pain caused by metastases to bone in cancer patients. The aim of this study was to investigate the analgesic effect of scutellarin on cancer-induced bone pain in rat models by intrathecal injection of Walker 256 carcinoma cells. Mechanical allodynia was determined by paw withdrawal threshold in response to mechanical stimulus, and thermal hyperalgesia was indicated by paw withdrawal latency in response to noxious thermal stimulus. The paw withdrawal threshold and paw withdrawal latencies were significantly decreased after inoculation of tumor cells, whereas administration of scutellarin significantly attenuated tumor cell inoculation-induced mechanical and heat hyperalgesia. Tumor cell inoculation-induced tumor growth was also significantly abrogated by scutellarin. Ca2+/calmodulin-dependent protein kinase II is a multifunctional kinase with up-regulated activity in bone pain models. The activation of Ca2+/calmodulin-dependent protein kinase II triggers phosphorylation of cAMP-response element binding protein. Scutellarin significantly reduced the expression of phosphorylated-Ca2+/calmodulin-dependent protein kinase II and phosphorylated-cAMP-response element binding protein in cancer-induced bone pain rats. Collectively, our study demonstrated that scutellarin attenuated tumor cell inoculation-induced bone pain by down-regulating the expression of phosphorylated-Ca2+/calmodulin-dependent protein kinase II and phosphorylated-cAMP-response element binding protein. The suppressive effect of scutellarin on phosphorylated-Ca2+/calmodulin-dependent protein kinase II/phosphorylated-cAMP-response element binding protein activation may serve as a novel therapeutic strategy for CIBP management.


Sign in / Sign up

Export Citation Format

Share Document