scholarly journals Big conductance calcium-activated potassium channel openers control spasticity without sedation

2017 ◽  
Vol 174 (16) ◽  
pp. 2662-2681 ◽  
Author(s):  
David Baker ◽  
Gareth Pryce ◽  
Cristina Visintin ◽  
Sofia Sisay ◽  
Alexander I Bondarenko ◽  
...  
Keyword(s):  
Potassium Channel ◽  
Potassium Channel Openers ◽  
Calcium Activated Potassium Channel

New Insights on KCa3.1 Channel Modulation

2020 ◽  
Vol 26 (18) ◽  
pp. 2096-2101
Author(s):  
Giuseppe Manfroni ◽  
Francesco Ragonese ◽  
Lorenzo Monarca ◽  
Andrea Astolfi ◽  
Loretta Mancinelli ◽  
...  
Keyword(s):  
Potassium Channel ◽  
Critical Role ◽  
Calcium Signalling ◽  
Typical Feature ◽  
Open Probability ◽  
Pharmacological Agents ◽  
Channel Modulation ◽  
Calcium Dependent ◽  
Modelling Techniques ◽  
Calcium Activated Potassium Channel

The human intermediate conductance calcium-activated potassium channel, KCa3.1, is involved in several pathophysiological conditions playing a critical role in cell secretory machinery and calcium signalling. The recent cryo-EM analysis provides new insights for understanding the modulation by both endogenous and pharmacological agents. A typical feature of this channel is the low open probability in saturating calcium concentrations and its modulation by potassium channel openers (KCOs), such as benzo imidazolone 1-EBIO, without changing calcium-dependent activation. In this paper, we proposed a model of KCOs action in the modulation of channel activity. The KCa3.1 channel has a very rich pharmacological profile with several classes of molecules that selectively interact with different binding sites of the channel. Among them, benzo imidazolones can be openers (positive modulators such as 1-EBIO, DC-EBIO) or blockers (negative modulators such as NS1619). Through computation modelling techniques, we identified the 1,4-benzothiazin-3-one as a promising scaffold to develop new KCa3.1 channel modulators. Further studies are needed to explore the potential use of 1-4 benzothiazine- 3-one in KCa3.1 modulation and its pharmacological application.

scholarly journals Effect of Potassium Channel Modulators on Morphine Withdrawal in Mice

2010 ◽  
Vol 4 ◽  
pp. SART.S6211 ◽  
Author(s):  
Vikas Seth ◽  
Mushtaq Ahmad ◽  
Prerna Upadhyaya ◽  
Monika Sharma ◽  
Vijay Moghe
Keyword(s):  
Potassium Channel ◽  
Withdrawal Syndrome ◽  
Channel Blocker ◽  
Inhibitory Effect ◽  
Morphine Withdrawal ◽  
The Other ◽  
Opioid Antagonist ◽  
Potassium Channel Openers ◽  
Potassium Channel Modulators ◽  
Withdrawal Signs

The present study was conducted to investigate the effect of potassium channel openers and blockers on morphine withdrawal syndrome. Mice were rendered dependent on morphine by subcutaneous injection of morphine; four hours later, withdrawal was induced by using an opioid antagonist, naloxone. Mice were observed for 30 minutes for the withdrawal signs ie, the characteristic jumping, hyperactivity, urination and diarrhea. ATP-dependent potassium (K+ATP) channel modulators were injected intraperitoneally (i.p.) 30 minutes before the naloxone. It was found that a K+ATP channel opener, minoxidil (12.5–50 mg/kg i.p.), suppressed the morphine withdrawal significantly. On the other hand, the K+ATP channel blocker glibenclamide (12.5–50 mg/kg i.p.) caused a significant facilitation of the withdrawal. Glibenclamide was also found to abolish the minoxidil's inhibitory effect on morphine withdrawal. The study concludes that K+ATP channels play an important role in the genesis of morphine withdrawal and K+ATP channel openers could be useful in the management of opioid withdrawal. As morphine opens K+ATP channels in neurons, the channel openers possibly act by mimicking the effects of morphine on neuronal K+ currents.

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