scholarly journals Inward rectifier potassium channels and a multitude of intracellular gating molecules

2000 ◽  
Vol 267 (19) ◽  
pp. 5823-5823 ◽  
Author(s):  
Thomas Baukrowitz
Keyword(s):  
Potassium Channels ◽  
Inward Rectifier ◽  
Inward Rectifier Potassium Channels

scholarly journals Pathologically Entangled: Brain trauma-evoked ROS imbalance disrupts Kir channel function in distant peripheral vessels

Function ◽  
2021 ◽  
Author(s):  
Nick Weir ◽  
Thomas A Longden
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Potassium Channels ◽  
Vascular Function ◽  
Inward Rectifier ◽  
Brain Trauma ◽  
Channel Function ◽  
Inward Rectifier Potassium Channels ◽  
Kir Channel

Abstract A Perspective on "Traumatic Brain Injury Impairs Systemic Vascular Function Through Disruption of Inward-Rectifier Potassium Channels"

scholarly journals Traumatic Brain Injury Impairs Systemic Vascular Function Through Disruption of Inward-Rectifier Potassium Channels

Function ◽  
2021 ◽  
Author(s):  
Adrian M Sackheim ◽  
Nuria Villalba ◽  
Maria Sancho ◽  
Osama F Harraz ◽  
Adrian D Bonev ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Potassium Channels ◽  
Signaling Pathways ◽  
Inward Rectifier ◽  
Pla2 Activity ◽  
Functional Responses ◽  
Channel Function ◽  
Inward Rectifier Potassium Channels ◽  
Kir2.1 Channel

Abstract Trauma can lead to widespread vascular dysfunction, but the underlying mechanisms remain largely unknown. Inward-rectifier potassium channels (Kir2.1) play a critical role in the dynamic regulation of regional perfusion and blood flow. Kir2.1 channel activity requires phosphatidylinositol 4,5-bisphosphate (PIP2), a membrane phospholipid that is degraded by phospholipase A2 (PLA2) in conditions of oxidative stress or inflammation. We hypothesized that PLA2–induced depletion of PIP2 after trauma impairs Kir2.1 channel function. A fluid percussion injury model of traumatic brain injury (TBI) in rats was used to study mesenteric resistance arteries 24 hours after injury. The functional responses of intact arteries were assessed using pressure myography. We analyzed circulating PLA2, hydrogen peroxide (H2O2), and metabolites to identify alterations in signaling pathways associated with PIP2 in TBI. Electrophysiology analysis of freshly-isolated endothelial and smooth muscle cells revealed a significant reduction of Ba2+-sensitive Kir2.1 currents after TBI. Additionally, dilations to elevated extracellular potassium and BaCl2- or ML 133-induced constrictions in pressurized arteries were significantly decreased following TBI, consistent with an impairment of Kir2.1 channel function. The addition of a PIP2 analog to the patch pipette successfully rescued endothelial Kir2.1 currents after TBI. Both H2O2 and PLA2 activity were increased after injury. Metabolomics analysis demonstrated altered lipid metabolism signaling pathways, including increased arachidonic acid, and fatty acid mobilization after TBI. Our findings support a model in which increased H2O2-induced PLA2 activity after trauma hydrolyzes endothelial PIP2, resulting in impaired Kir2.1 channel function.

scholarly journals WIN55,212-2, a Dual Modulator of Cannabinoid Receptors and G Protein-Coupled Inward Rectifier Potassium Channels

Biomedicines ◽  
2021 ◽  
Vol 9 (5) ◽  
pp. 484
Author(s):  
Dongchen An ◽  
Steve Peigneur ◽  
Jan Tytgat
Keyword(s):  
Potassium Channels ◽  
Potassium Channel ◽  
G Protein ◽  
Cannabinoid Receptors ◽  
Inward Rectifier ◽  
Xenopus Laevis Oocyte ◽  
Inward Rectifier Potassium Channels ◽  
Wide Range ◽  
Cb2 Receptors ◽  
G Protein Coupled

The coupling of cannabinoid receptors, CB1 and CB2, to G protein-coupled inward rectifier potassium channels, GIRK1 and GIRK2, modulates neuronal excitability in the human brain. The present study established and validated the functional expression in a Xenopus laevis oocyte expression system of CB1 and CB2 receptors, interacting with heteromeric GIRK1/2 channels and a regulator of G protein signaling, RGS4. This ex vivo system enables the discovery of a wide range of ligands interacting orthosterically or allosterically with CB1 and/or CB2 receptors. WIN55,212-2, a non-selective agonist of CB1 and CB2, was used to explore the CB1- or CB2-GIRK1/2-RGS4 signaling cascade. We show that WIN55,212-2 activates CB1 and CB2 at low concentrations whereas at higher concentrations it exerts a direct block of GIRK1/2. This illustrates a dual modulatory function, a feature not described before, which helps to explain the adverse effects induced by WIN55,212-2 in vivo. When comparing the effects with other typical cannabinoids such as Δ9-THC, CBD, CP55,940, and rimonabant, only WIN55,212-2 can significantly block GIRK1/2. Interestingly, the inward rectifier potassium channel, IRK1, a non-G protein-coupled potassium channel important for setting the resting membrane voltage and highly similar to GIRK1 and GIRK2, is not sensitive to WIN55,212-2, Δ9-THC, CBD, CP55,940, or rimonabant. From this, it is concluded that WIN55,212-2 selectively blocks GIRK1/2.

Functional Evidence for Inward-Rectifier Potassium Channels in Rat Cremaster Muscle Arterioles

2000 ◽  
Vol 59 (1) ◽  
pp. 1-6 ◽  
Author(s):  
Alex L. Loeb ◽  
Ildikó Go˝de´ny ◽  
David E. Longnecker
Keyword(s):  
Potassium Channels ◽  
Inward Rectifier ◽  
Cremaster Muscle ◽  
Inward Rectifier Potassium Channels

Molecular and Functional Heterogeneity of Inward Rectifier Potassium Channels in the Brain and Heart

1996 ◽  
pp. 59-67
Author(s):  
Naohiko Takahashi ◽  
Ken-Ichirou Morishige ◽  
Mitsuhiko Yamada ◽  
Chikako Kondo ◽  
Yoshihisa Kurachi
Keyword(s):  
Potassium Channels ◽  
Inward Rectifier ◽  
Functional Heterogeneity ◽  
Inward Rectifier Potassium Channels ◽  
The Brain

scholarly journals Influence of chronic alcohol consumption on inward rectifier potassium channels in cerebral arterioles

2008 ◽  
Vol 75 (3) ◽  
pp. 367-372 ◽  
Author(s):  
Hong Sun ◽  
Honggang Zhao ◽  
Glenda M. Sharpe ◽  
Denise M. Arrick ◽  
William G. Mayhan
Keyword(s):  
Alcohol Consumption ◽  
Potassium Channels ◽  
Inward Rectifier ◽  
Chronic Alcohol ◽  
Chronic Alcohol Consumption ◽  
Inward Rectifier Potassium Channels ◽  
Cerebral Arterioles
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