Determinants of the repetitive-CMAP occurrence and therapy efficacy in slow-channel myasthenia
1区 · 医学
作者: Di, Li ; Chen, Hai ; Lu, Yan ; Selcen, Duygu ; Engel, Andrew G. ; Da, Yuwei ; Shen, Xin-Ming
To find determinants of the occurrence of repetitive compound muscle action potential (R-CMAP) and to assess the efficacy of channel blocker therapy in slow-channel congenital myasthenic syndrome (SCCMS).
Neurologic examination, EMG study, laboratory test, muscle biopsy, and next-generation and Sanger sequencing; literature review of reported patients with SCCMS, including EMG, kinetics of mutant acetylcholine receptors (AChRs), and response to therapy; and simulation of the decay phase of endplate potential (EPP) were performed.
Three newly characterized and 57 reported patients with SCCMS with mutations of AChR subunits were included. In patients with R-CMAP, the length of channel opening bursts of mutant AChR was increased 8.68 ± 2.82 (mean ± SD)-fold compared to wild-type; in patients without R-CMAP, the length was increased 3.84 ± 0.65-fold (95% confidence interval 3.18-6.50, p = 0.000014). The EPP amplitude after refractory period of action potential in muscle fiber is above the threshold in patients with R-CMAP but below the threshold in patients without R-CMAP. In patients with good results from channel blocker therapy, treatment was initiated 11.60 ± 5.17 years after onset of symptoms; in patients with no to moderate benefit from channel blocker therapy, treatment was initiated 30.70 ± 12.72 years after onset (95% confidence interval -28.57 to -9.63, p = 0.00089).
In SCCMS, the R-CMAP occurrence is related to the extent of prolongation of the opening episodes of mutant AChR channel. Channel blocker treatment is more effective the sooner it is started after the onset of symptoms.
CLASSIFICATION OF EVIDENCE:
This study provides Class IV evidence that channel blocker therapy in patients with SCCMS improves symptoms.
2019-07-01·Protoplasma3区 · 生物学
Glutamate signaling enhances the heat tolerance of maize seedlings by plant glutamate receptor-like channels-mediated calcium signaling.
3区 · 生物学
作者: Zhong-Guang Li ; Xin-Yu Ye ; Xue-Mei Qiu
Glutamate (Glu), a neurotransmitter in animal, is a novel signaling molecule in plants, which takes part in cellular metabolism, seed germination, plant growth, development, and long-distance information transfer. However, whether Glu can enhance the heat tolerance in maize seedlings and its relation to calcium signaling is still elusive. In this study, maize seedlings were pretreated with Glu and then exposed to heat stress. The results showed that Glu pretreatment enhanced the survival percentage of maize seedlings under heat tolerance, indicating that Glu could increase the heat tolerance of maize seedlings. The Glu-induced heat tolerance was weakened by exogenous calcium chloride, plasma membrane Ca2+ channel blocker (LaCl3), Ca2+ chelator (ethylene glycol-bis(b-aminoethylether)-N,N, N΄,N΄-tetraacetic acid), calmodulin antagonists (trifluoperazine and chlopromazine), and plant glutamate receptor-like antagonists (MgCl2 and 6,7-dinitroquinoxaline- 2,3-(1H,4H)- dione). These findings for the first time reported that Glu could increase the heat tolerance of maize seedlings by plant glutamate receptor-like channels-mediated calcium signaling.
2017-10-01·Pesticide biochemistry and physiology2区 · 生物学
Attribution of Bax and mitochondrial permeability transition pore on cantharidin-induced apoptosis of Sf9 cells.
2区 · 生物学
作者: Gaofeng Cui ; Yuansheng Li ; Kai Ding ; Shaodong Hao ; Jinzhong Wang ; Zhiyong Zhang
To investigate the insecticidal mechanism of cantharidin, a promising biological pesticide substance from blister beetle, on Sf9 cells, a cultured cell line derived from fall armyworm, Spodoptera frugiperda, we preliminary studied the attribution of Bax channel and mitochondrial permeability transition pore on cantharidin-induced mitochondrial apoptosis signal pathway. Changes in cell morphology, activity of mitochondrial dehydrogenases, release of cytochrome C and mitochondrial transmembrane potential were detected when the two channels were blocked by specific inhibitors, Bax channel blocker and cyclosporin A. Results showed that cantharidin-induced apoptotic features, including changes in the cell morphology, release of cytochrome C and decrease in mitochondrial transmembrane potential could be significantly inhibited by Bax channel blocker, while cyclosporin A accelerated the downward trend of mitochondrial dehydrogenases activity and caused a decrease of Ca2+ in mitochondria. In summary, Bax might be necessary but not exclusively for the apoptosis induced by cantharidin and the attribution of these channels seems to be more complexity.