Article
Biochemistry & Molecular Biology
Gonzalo Ferreira, Axel Santander, Romina Cardozo, Luisina Chavarria, Lucia Dominguez, Nicolas Mujica, Milagros Benitez, Santiago Sastre, Luis Sobrevia, Garth L. Nicolson
Summary: Inwardly rectifying potassium (Kir) channels are important for maintaining membrane potential and potassium homeostasis. These channels have various subtypes and can be regulated by molecules found in nutrients, such as phosphoinositols, polyamines, and Mg2+. Changes in Kir channels can affect metabolism and the ability to absorb nutrients and electrolytes. The study of nutrigenomics of ion channels is crucial for understanding how diet and nutrients can impact ion channel function, expression, and lead to pathological conditions that affect diet and electrolyte intake.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2023)
Review
Cardiac & Cardiovascular Systems
Louise Reilly, Lee L. Eckhardt
Summary: The potassium inward rectifier channel Kir2 is crucial for cardiac repolarization and membrane stability. Mutations in related genes can lead to sudden cardiac death syndromes. Research focuses on the structure, physiology, and pharmacology of Kir2 channels, as well as their implications for atrial fibrillation treatment and drug safety testing.
Article
Medicine, Research & Experimental
Claire A. Ruddiman, Richard Peckham, Melissa A. Luse, Yen-Lin Chen, Maniselvan Kuppusamy, Bruce A. Corliss, P. Jordan Hall, Chien-Jung Lin, Shayn M. Peirce, Swapnil K. Sonkusare, Robert P. Mecham, Jessica E. Wagenseil, Brant E. Isakson
Summary: The study investigates lipid regulation of the endothelial Kir2.1 channel and its contribution to vasodilation in resistance arteries. It is found that phosphatidylserine (PS) competes with phosphatidylinositol 4,5-bisphosphate (PIP2) binding on Kir2.1, and PS blocks PIP2 activation of Kir2.1 in HEK cells and resistance arteries. The localization of intracellular lipids within the endothelium is an important determinant of vascular function.
Article
Multidisciplinary Sciences
Grigory Maksaev, Michael Bruendl-Jirout, Anna Stary-Weinzinger, Eva-Maria Zangerl-Plessl, Sun-Joo Lee, Colin G. Nichols
Summary: The authors introduced negative charges in Kir2.2 channels, resulting in pH-dependent sub-conductances. Molecular dynamics simulations show that protonation leads to step-wise alterations of ion pooling and conductance, appearing as gated substates. Single-channel recordings reveal pH-dependent subconductance behaviors.
NATURE COMMUNICATIONS
(2023)
Review
Cardiac & Cardiovascular Systems
Maria Sancho, Jacob Fletcher, Donald G. Welsh
Summary: Cerebral arteries contain two cell types, smooth muscle cells (SMCs) and endothelial cells (ECs), that can sense specific hemodynamic forces to regulate arterial tone and brain perfusion. This review focuses on the Kir2 channels in vascular tissues and their regulation by membrane lipids, phosphatidylinositol 4,5-bisphosphate (PIP2) and cholesterol, as well as their interaction with caveolin-1 (Cav1) and syntrophin to confer hemodynamic sensitivity.
FRONTIERS IN CARDIOVASCULAR MEDICINE
(2022)
Article
Chemistry, Multidisciplinary
Collin G. Borcik, Isaac R. Eason, Maryam Yekefallah, Reza Amani, Ruixian Han, Boden H. Vanderloop, Benjamin J. Wylie
Summary: Cholesterol oligomers are found in various membrane protein crystal structures, but their biological function is not well understood. This study presents the structural and functional details of a cholesterol dimer that stabilizes the inactivated state of an inward-rectifier potassium channel. The findings provide insights into the role of cholesterol oligomers in regulating channel conductance.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Pharmacology & Pharmacy
Akimasa Iijima, Olga Svecova, Jan Hosek, Roman Kula, Marketa Bebarova
Summary: This study found that sildenafil, the orally administered drug for treating erectile dysfunction, could inhibit both the inward and outward current components of the ventricular IK1 channels in the human body, which may contribute to arrhythmias. Additionally, low concentrations of the environmental contaminant Ba2+ can enhance the inhibitory effect of sildenafil on these channels, leading to increased risk of cardiac repolarization delay.
FRONTIERS IN PHARMACOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Chunshu Li, Yan Yang
Summary: This paper reviews the role of inward rectifier potassium channels (Kir channels) in maintaining the resting membrane potential, signal transduction, and connecting metabolism and membrane excitability. It highlights the close relationship between Kir channels and normal physiological functions as well as the occurrence and development of certain diseases. The functional expression of Kir channels in vascular endothelial cells and smooth muscle cells, and their changes in disease states are discussed, with a particular focus on recent research progress in stem cells. The aim is to deepen our understanding of Kir channels in vascular tissues and provide new ideas and directions for the treatment of related ion channel diseases.
Review
Cell Biology
Katie M. Beverley, Bikash R. Pattnaik
Summary: This article discusses the potential roles of Kir channels in the retina and their connections with the functions of other tissues. Studies on the expression of KCNJ genes have identified the presence of all subclasses of Kir channels in the retina and RPE. However, the inconsistency between the expression of subtype genes and protein expression remains a mystery. The use of multiomics or functional omics approaches can shed light on posttranscriptional changes that may influence Kir subunit mRNA translation in the retina.
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
(2022)
Article
Pharmacology & Pharmacy
Martin Machacek, Olga Svecova, Marketa Bebarova
Summary: The study found that sildenafil significantly inhibits IK1 at certain concentrations, and the inhibition effect is more pronounced when used in combination with Ba2+. This combined effect leads to a significant prolongation of action potential duration, potentially contributing to arrhythmias in patients treated with sildenafil.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Neurosciences
Fei Luo, Ting Wang, Jun-yong Deng, Xiao-dan Luo
Summary: Orexin, a neuropeptide synthesized in the hypothalamus, modulates brain activity and is involved in psychiatric disorders. This study found that orexin enhances GABAergic transmission onto mPFC pyramidal neurons by inhibiting inward rectifier K+ channels on Sst interneurons, further depolarizing the interneurons and increasing Ca2+ influx through T-type Ca2+ channels.
EXPERIMENTAL NEUROLOGY
(2023)
Article
Biochemistry & Molecular Biology
Dongchen An, Steve Peigneur, Jan Tytgat
Summary: 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. WIN55,212-2, a non-selective agonist of CB1 and CB2, activates CB1 and CB2 at low concentrations and blocks GIRK1/2 at high concentrations.
Article
Biochemistry & Molecular Biology
Manuel Nieves-Cordones, Farrukh Azeem, Yuchen Long, Martin Boeglin, Geoffrey Duby, Karine Mouline, Eric Hosy, Alain Vavasseur, Isabelle Cherel, Thierry Simonneau, Frederic Gaymard, Jeffrey Leung, Isabelle Gaillard, Jean-Baptiste Thibaud, Anne-Alienor Very, Arezki Boudaoud, Herve Sentenac
Summary: Gas exchange in land plants is regulated by stomata, which optimize photosynthesis and limit water vapor loss. This study reveals the mechanical contributions of epidermal cells in stomatal aperture regulation. By disrupting the Arabidopsis thaliana K+ channel subunit gene AtKC1, the researchers found that the back pressure exerted by pavement cells onto guard cells is impaired, leading to larger stomatal apertures. Potassium ion transport within the leaf epidermis plays a crucial role in stomatal functioning.
Article
Chemistry, Medicinal
Dongchen An, Ernesto Lopes Pinheiro-Junior, Laszlo Beress, Irina Gladkikh, Elena Leychenko, Eivind A. B. Undheim, Steve Peigneur, Jan Tytgat
Summary: AsKC11, a Kunitz peptide found in the venom of A. sulcata, is the first peptide shown to directly activate neuronal GIRK1/2 channels independent from Gi/o protein activity, without affecting the inward-rectifier potassium channel (IRK1) and with only a minor effect on K(V)1.6 channels. Thus, AsKC11 is a novel activator of GIRK channels resulting in larger K+ currents because of an increased chord conductance.
Article
Cardiac & Cardiovascular Systems
Sara Ballouz, Melissa M. Mangala, Matthew D. Perry, Stewart Heitmann, Jesse A. Gillis, Adam P. Hill, Jamie Vandenberg
Summary: The study identified a strong correlation between CACNA1C (L-type calcium current) and KCNH2 (rapid delayed rectifier K+ current) expression in human hearts, which could limit variability in action potential duration and reduce susceptibility to arrhythmia. This co-expression also increased the robustness of cardiac electrical activity.
CARDIOVASCULAR RESEARCH
(2021)