scholarly journals Calcium-Activated Potassium Channel Inhibition in Autonomically Stimulated Human Atrial Myocytes.

2019 ◽  
Author(s):  
Chiara Celotto ◽  
Carlos Sánchez ◽  
Pablo Laguna ◽  
Esther Pueyo
Keyword(s):  
Potassium Channel ◽  
Atrial Myocytes ◽  
Human Atrial Myocytes ◽  
Channel Inhibition ◽  
Calcium Activated Potassium Channel

scholarly journals Ginkgo biloba L. Prevents Hypobaric Hypoxia–Induced Spatial Memory Deficit Through Small Conductance Calcium-Activated Potassium Channel Inhibition: The Role of ERK/CaMKII/CREB Signaling

2021 ◽  
Vol 12 ◽  
Author(s):  
Neetu Kushwah ◽  
Vishal Jain ◽  
Manisha Kadam ◽  
Rahul Kumar ◽  
Aastha Dheer ◽  
...  
Keyword(s):  
Potassium Channel ◽  
Signaling Pathway ◽  
Ginkgo Biloba ◽  
Cognitive Functions ◽  
Memory Impairment ◽  
Hypobaric Hypoxia ◽  
Glutamate Excitotoxicity ◽  
Channel Inhibition ◽  
Calcium Activated Potassium Channel ◽  
Small Conductance

Hypobaric hypoxia (HH) is a stressful condition, which is more common at high altitudes and can impair cognitive functions. Ginkgo biloba L. leaf extract (GBE) is widely used as herbal medicine against different disorders. Its ability to improve cognitive functions, reduce oxidative stress, and promote cell survival makes it a putative therapeutic candidate against HH. The present study has been designed to explore the effect of GBE on HH-induced neurodegeneration and memory impairment as well as possible signaling mechanisms involved. 220–250 gm (approximately 6- to 8-week-old) Sprague Dawley rats were randomly divided into different groups. GBE was orally administered to respective groups at a dose of 100 mg/kg/day throughout the HH exposure, i.e., 14 days. Memory testing was performed followed by hippocampus isolation for further processing of different molecular and morphological parameters related to cognition. The results indicated that GBE ameliorates HH-induced memory impairment and oxidative damage and reduces apoptosis. Moreover, GBE modulates the activity of the small conductance calcium-activated potassium channels, which further reduces glutamate excitotoxicity and apoptosis. The exploration of the downstream signaling pathway demonstrated that GBE administration prevents HH-induced small conductance calcium-activated potassium channel activation, and that initiates pro-survival machinery by activating extracellular signal–regulated kinase (ERK)/calmodulin-dependent protein kinase II (CaMKII) and the cAMP response element–binding protein (CREB) signaling pathway. In summary, the current study demonstrates the beneficial effect of GBE on conditions like HH and provides various therapeutic targets involved in the mechanism of action of GBE-mediated neuroprotection.

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.

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