scholarly journals Simulation of Ca-Calmodulin-Dependent Protein Kinase II on Rabbit Ventricular Myocyte Ion Currents and Action Potentials

2007 ◽  
Vol 93 (11) ◽  
pp. 3835-3847 ◽  
Author(s):  
Eleonora Grandi ◽  
Jose L. Puglisi ◽  
Stefan Wagner ◽  
Lars S. Maier ◽  
Stefano Severi ◽  
...  
1997 ◽  
Vol 78 (1) ◽  
pp. 409-416 ◽  
Author(s):  
Keiko Nakanishi ◽  
Fan Zhang ◽  
Douglas A. Baxter ◽  
Arnold Eskin ◽  
John H. Byrne

Nakanishi, Keiko, Fan Zhang, Douglas A. Baxter, Arnold Eskin, and John H. Byrne. Role of calcium-calmodulin–dependent protein kinase II in modulation of sensorimotor synapses in Aplysia. J. Neurophysiol. 78: 409–416, 1997. The Ca2+-calmodulin–dependent protein kinase II (CaMKII) inhibitor, {1-[N,O - bis(5 - isoquinolinesulfonyl) - N - methyl - L - tyrosyl] - 4 - phenylpiper azine} (KN-62), was used to investigate the role of CaMKII in synaptic transmission and serotonin (5-HT)-induced facilitation in Aplysia. Application of KN-62 (10 μM) by itself increased the amplitude of excitatory postsynaptic potentials (EPSPs) at sensorimotor synapses in pleural-pedal ganglia. Moreover, in the presence of KN-62, 5-HT–induced short-term facilitation was attenuated. Application of KN-62 by itself slightly increased the duration of action potentials in isolated sensory neuron somata but did not block spike broadening produced by 5-HT. KN-62 had no effect on excitability of isolated sensory neuron somata nor did it block 5-HT–induced enhancement of excitability. These results indicate that the attenuation of short-term facilitation by KN- 62 is not due to modulation of the membrane currents contributing to 5-HT–induced spike broadening or enhancement of excitability. Rather, these data are consistent with the hypothesis that CaMKII contributes to the regulation of sensorimotor connections and that it has a role in spike-duration–independent processes contributing to short-term facilitation.


2021 ◽  
Vol 17 (1) ◽  
pp. e1008624
Author(s):  
Vikas Pandey ◽  
Lai-Hua Xie ◽  
Zhilin Qu ◽  
Zhen Song

Mitochondria are vital organelles inside the cell and contribute to intracellular calcium (Ca2+) dynamics directly and indirectly via calcium exchange, ATP generation, and production of reactive oxygen species (ROS). Arrhythmogenic Ca2+ alternans in cardiac myocytes has been observed in experiments under abnormal mitochondrial depolarization. However, complex signaling pathways and Ca2+ cycling between mitochondria and cytosol make it difficult in experiments to reveal the underlying mechanisms of Ca2+ alternans under abnormal mitochondrial depolarization. In this study, we use a newly developed spatiotemporal ventricular myocyte computer model that integrates mitochondrial Ca2+ cycling and complex signaling pathways to investigate the mechanisms of Ca2+ alternans during mitochondrial depolarization. We find that elevation of ROS in response to mitochondrial depolarization plays a critical role in promoting Ca2+ alternans. Further examination reveals that the redox effect of ROS on ryanodine receptors and sarco/endoplasmic reticulum Ca2+-ATPase synergistically promote alternans. Upregulation of mitochondrial Ca2+ uniporter promotes Ca2+ alternans via Ca2+-dependent mitochondrial permeability transition pore opening. Due to their relatively slow kinetics, oxidized Ca2+/calmodulin-dependent protein kinase II activation and ATP do not play significant roles acutely in the genesis of Ca2+ alternans after mitochondrial depolarization, but their roles can be significant in the long term, mainly through their effects on sarco/endoplasmic reticulum Ca2+-ATPase activity. In conclusion, mitochondrial depolarization promotes Ca2+ alternans acutely via the redox effect of ROS and chronically by ATP reduction. It suppresses Ca2+ alternans chronically through oxidized Ca2+/calmodulin-dependent protein kinase II activation.


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.


1998 ◽  
Vol 67 (2) ◽  
pp. 145-152 ◽  
Author(s):  
Wendy W. Waters ◽  
Pat L. Chen ◽  
Newell H. McArthur ◽  
Pete A. Moreno ◽  
Paul G. Harms

Sign in / Sign up

Export Citation Format

Share Document