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bk channel pharmacology

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https://www.readbyqxmd.com/read/28724979/impairment-of-coronary-endothelial-function-by-hypoxia-reoxygenation-involves-trpc3-inhibition-mediated-kca-channel-dysfunction-implication-in-ischemia-reperfusion-injury
#1
Xiang-Chong Wang, Wen-Tao Sun, Jie Fu, Jun-Hao Huang, Cheuk-Man Yu, Malcolm John Underwood, Guo-Wei He, Qin Yang
Despite increasing knowledge of the significance of calcium-activated potassium (KCa) and canonical transient receptor potential (TRPC) channels in endothelial physiology, no studies so far have investigated the link between these two distinct types of channels in the control of vascular tone in pathological conditions. We previously demonstrated that hypoxia-reoxygenation (H-R) inhibits endothelial KCa and TRPC3 channels in porcine coronary arteries (PCAs). The present study further investigated whether modulation of TRPC3 is involved in H-R-induced KCa channel inhibition and associated vasodilatory dysfunction using approaches of wire myography, whole-cell voltage-clamp, and coimmunoprecipitation...
July 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28693898/nanosecond-pulsed-electric-fields-depolarize-transmembrane-potential-via-voltage-gated-k-ca-2-and-trpm8-channels-in-u87-glioblastoma-cells
#2
Ryan C Burke, Sylvia M Bardet, Lynn Carr, Sergii Romanenko, Delia Arnaud-Cormos, Philippe Leveque, Rodney P O'Connor
Nanosecond pulsed electric fields (nsPEFs) have a variety of applications in the biomedical and biotechnology industries. Cancer treatment has been at the forefront of investigations thus far as nsPEFs permeabilize cellular and intracellular membranes leading to apoptosis and necrosis. nsPEFs may also influence ion channel gating and have the potential to modulate cell physiology without poration of the membrane. This phenomenon was explored using live cell imaging and a sensitive fluorescent probe of transmembrane voltage in the human glioblastoma cell line, U87 MG, known to express a number of voltage-gated ion channels...
July 8, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28600454/the-slo-w-path-to-identifying-the-mitochondrial-channels-responsible-for-ischemic-protection
#3
REVIEW
Charles Owen Smith, Keith Nehrke, Paul S Brookes
Mitochondria play an important role in tissue ischemia and reperfusion (IR) injury, with energetic failure and the opening of the mitochondrial permeability transition pore being the major causes of IR-induced cell death. Thus, mitochondria are an appropriate focus for strategies to protect against IR injury. Two widely studied paradigms of IR protection, particularly in the field of cardiac IR, are ischemic preconditioning (IPC) and volatile anesthetic preconditioning (APC). While the molecular mechanisms recruited by these protective paradigms are not fully elucidated, a commonality is the involvement of mitochondrial K(+) channel opening...
June 9, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28468834/a-voltage-dependent-k-channel-in-the-lysosome-is-required-for-refilling-lysosomal-ca-2-stores
#4
Wuyang Wang, Xiaoli Zhang, Qiong Gao, Maria Lawas, Lu Yu, Xiping Cheng, Mingxue Gu, Nirakar Sahoo, Xinran Li, Ping Li, Stephen Ireland, Andrea Meredith, Haoxing Xu
The resting membrane potential (Δψ) of the cell is negative on the cytosolic side and determined primarily by the plasma membrane's selective permeability to K(+) We show that lysosomal Δψ is set by lysosomal membrane permeabilities to Na(+) and H(+), but not K(+), and is positive on the cytosolic side. An increase in juxta-lysosomal Ca(2+) rapidly reversed lysosomal Δψ by activating a large voltage-dependent and K(+)-selective conductance (LysoKVCa). LysoKVCa is encoded molecularly by SLO1 proteins known for forming plasma membrane BK channels...
June 5, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28455309/molecular-structure-and-function-of-big-calcium-activated-potassium-channels-in-skeletal-muscle-pharmacological-perspectives
#5
Fatima Maqoud, Michela Cetrone, Antonietta Mele, Domenico Tricarico
The large-conductance Ca(2+)-activated K(+) (BK) channel is broadly expressed in various mammalian cells and tissues such as neurons, skeletal muscles (sarco-BK), and smooth muscles. These channels are activated by changes in membrane electrical potential and by increases in the concentration of intracellular calcium ion (Ca(2+)). The large-conductance Ca(2+)-activated K(+) (BK) channel is subjected to many mechanisms that add diversity to the BK channel α subunit gene. These channels are indeed subject to alternative splicing, auxiliary subunits modulation, post-translational modifications and protein-protein interactions...
April 28, 2017: Physiological Genomics
https://www.readbyqxmd.com/read/28116849/pharmacological-approach-to-understanding-the-control-of-insulin-secretion-in-human-islets
#6
Jean-Claude Henquin, Denis Dufrane, Valery Gmyr, Julie Kerr-Conte, Myriam Nenquin
AIMS: To understand better the control of insulin secretion by human β cells and to identify similarities to and differences from rodent models. METHODS: Dynamic insulin secretion was measured in perifused human islets treated with pharmacological agents of known modes of action. RESULTS: Glucokinase activation (Ro28-1675) lowered the glucose threshold for stimulation of insulin secretion to 1 mmol/L (G1), augmented the response to G3-G5 but not to G8-G15, whereas tolbutamide remained active in G20, which indicates that not all KATP channels were closed by high glucose concentrations...
January 24, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/27823962/the-transient-receptor-potential-ankyrin-1-mediates-mechanical-hyperalgesia-induced-by-the-activation-of-b1-receptor-in-mice
#7
Flavia Carla Meotti, Cláudia Pinto Figueiredo, Marianne Manjavachi, João B Calixto
The kinin receptor B1 and the transient receptor potential ankyrin 1 (TRPA1) work as initiators and gatekeepers of nociception and inflammation. This study reports that the nociceptive transmission induced by activation of B1 receptor is dependent on TRPA1 ion channel. The mechanical hyperalgesia was induced by intrathecal (i.t.) injection of B1 agonist des-Arginine(9)-bradykinin (DABK) or TRPA1 agonist cinnamaldehyde and was evaluated by the withdrawal response after von Frey Hair application in the hind paw...
February 1, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/27807200/molecular-determinants-of-bk-channel-functional-diversity-and-functioning
#8
REVIEW
Ramon Latorre, Karen Castillo, Willy Carrasquel-Ursulaez, Romina V Sepulveda, Fernando Gonzalez-Nilo, Carlos Gonzalez, Osvaldo Alvarez
Large-conductance Ca(2+)- and voltage-activated K(+) (BK) channels play many physiological roles ranging from the maintenance of smooth muscle tone to hearing and neurosecretion. BK channels are tetramers in which the pore-forming α subunit is coded by a single gene (Slowpoke, KCNMA1). In this review, we first highlight the physiological importance of this ubiquitous channel, emphasizing the role that BK channels play in different channelopathies. We next discuss the modular nature of BK channel-forming protein, in which the different modules (the voltage sensor and the Ca(2+) binding sites) communicate with the pore gates allosterically...
2017: Physiological Reviews
https://www.readbyqxmd.com/read/27806944/the-mechanosensitive-bk%C3%AE-%C3%AE-1-channel-localizes-to-cilia-of-principal-cells-in-rabbit-cortical-collecting-duct-ccd
#9
Rolando Carrisoza-Gaytán, Lijun Wang, Carlos Schreck, Thomas R Kleyman, Wen-Hui Wang, Lisa M Satlin
Within the CCD of the distal nephron of the rabbit, the BK (maxi K) channel mediates Ca(2+)- and/or stretch-dependent flow-induced K(+) secretion (FIKS) and contributes to K(+) adaptation in response to dietary K(+) loading. An unresolved question is whether BK channels in intercalated cells (ICs) and/or principal cells (PCs) in the CCD mediate these K(+) secretory processes. In support of a role for ICs in FIKS is the higher density of immunoreactive apical BKα (pore-forming subunit) and functional BK channel activity than detected in PCs, and an increase in IC BKα expression in response to a high-K(+) diet...
January 1, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/27806708/ryanodine-induced-vasoconstriction-of-the-gerbil-spiral-modiolar-artery-depends-on-the-ca-2-sensitivity-but-not-on-ca-2-sparks-or-bk-channels
#10
Gayathri Krishnamoorthy, Katrin Reimann, Philine Wangemann
BACKGROUND: In many vascular smooth muscle cells (SMCs), ryanodine receptor-mediated Ca(2+) sparks activate large-conductance Ca(2+)-activated K(+) (BK) channels leading to lowered SMC [Ca(2+)]i and vasodilation. Here we investigated whether Ca(2+) sparks regulate SMC global [Ca(2+)]i and diameter in the spiral modiolar artery (SMA) by activating BK channels. METHODS: SMAs were isolated from adult female gerbils, loaded with the Ca(2+)-sensitive flourescent dye fluo-4 and pressurized using a concentric double-pipette system...
November 2, 2016: BMC Physiology
https://www.readbyqxmd.com/read/27747371/estradiol-modified-prolactin-secretion-independently-of-action-potentials-and-ca-2-and-blockade-of-outward-potassium-currents-in-gh3-cells
#11
Manuel Sánchez, Lorena Suárez, Begoña Cantabrana, Javier Bordallo
Estrogens facilitate prolactin (PRL) secretion acting on pituitary cells. In GH3 cells, estradiol induces acute action potentials and oscillations of intracellular Ca(2+) associated with the secretagogue function. Estradiol modulates several ion channels which may affect the action potential rate and the release of PRL in lactotroph cells, which might depend on its concentration. The aims were to characterize the acute effect of supraphysiological concentrations of estradiol on Ca(2+) and noninactivating K(+) currents and measure the effect on the spontaneous action potentials and PRL release in the somatolactotroph cell line, GH3...
January 2017: Naunyn-Schmiedeberg's Archives of Pharmacology
https://www.readbyqxmd.com/read/27690717/the-glycosylation-of-the-extracellular-loop-of-%C3%AE-2-subunits-diversifies-functional-phenotypes-of-bk-channels
#12
Zhi-Gang Huang, Hao-Wen Liu, Zhen-Zhen Yan, Sheng Wang, Lu-Yang Wang, Jiu-Ping Ding
Large-conductance Ca(2+)- and voltage-activated potassium (MaxiK or BK) channels are composed of a pore-forming α subunit (Slo) and 4 types of auxiliary β subunits or just a pore-forming α subunit. Although multiple N-linked glycosylation sites in the extracellular loop of β subunits have been identified, very little is known about how glycosylation influences the structure and function of BK channels. Using a combination of site-directed mutagenesis, western blot and patch-clamp recordings, we demonstrated that 3 sites in the extracellular loop of β2 subunit are N-glycosylated (N-X-T/S at N88, N96 and N119)...
March 4, 2017: Channels
https://www.readbyqxmd.com/read/27605581/testosterone-decreases-urinary-bladder-smooth-muscle-excitability-via-novel-signaling-mechanism-involving-direct-activation-of-the-bk-channels
#13
Kiril L Hristov, Shankar P Parajuli, Aaron Provence, Georgi V Petkov
In addition to improving sexual function, testosterone has been reported to have beneficial effects in ameliorating lower urinary tract symptoms by increasing bladder capacity and compliance, while decreasing bladder pressure. However, the cellular mechanisms by which testosterone regulates detrusor smooth muscle (DSM) excitability have not been elucidated. Here, we used amphotericin-B perforated whole cell patch-clamp and single channel recordings on inside-out excised membrane patches to investigate the regulatory role of testosterone in guinea pig DSM excitability...
December 1, 2016: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/27574914/coronary-arterial-bk-channel-dysfunction-exacerbates-ischemia-reperfusion-induced-myocardial-injury-in-diabetic-mice
#14
Tong Lu, Bin Jiang, Xiao-Li Wang, Hon-Chi Lee
The large conductance Ca(2+)-activated K(+) (BK) channels, abundantly expressed in coronary artery smooth muscle cells (SMCs), play a pivotal role in regulating coronary circulation. A large body of evidence indicates that coronary arterial BK channel function is diminished in both type 1 and type 2 diabetes. However, the consequence of coronary BK channel dysfunction in diabetes is not clear. We hypothesized that impaired coronary BK channel function exacerbates myocardial ischemia/reperfusion (I/R) injury in streptozotocin-induced diabetic mice...
September 2016: Applied Physiology, Nutrition, and Metabolism, Physiologie Appliquée, Nutrition et Métabolisme
https://www.readbyqxmd.com/read/27455901/effects-of-k-channel-openers-on-spontaneous-action-potentials-in-detrusor-smooth-muscle-of-the-guinea-pig-urinary-bladder
#15
Hiroaki Takagi, Hikaru Hashitani
The modulation of spontaneous excitability in detrusor smooth muscle (DSM) upon the pharmacological activation of different populations of K(+) channels was investigated. Effects of distinct K(+) channel openers on spontaneous action potentials in DSM of the guinea-pig bladder were examined using intracellular microelectrode techniques. NS1619 (10μM), a large conductance Ca(2+)-activated K(+) (BK) channel opener, transiently increased action potential frequency and then prevented their generation without hyperpolarizing the membrane in a manner sensitive to iberiotoxin (IbTX, 100nM)...
October 15, 2016: European Journal of Pharmacology
https://www.readbyqxmd.com/read/27238271/developing-molecular-pharmacology-of-bk-channels-for-therapeutic-benefit
#16
G J Kaczorowski, M L Garcia
High conductance, calcium-activated potassium (BK) channels (KCa1.1) are important in regulating physiologic responses in many types of tissues and, as such, present opportunities for development of new therapeutic agents. Both channel agonists and inhibitors could have therapeutic utility, depending on medical application under consideration. However, characterization of molecular pharmacology of BK channels is incomplete and has been difficult to accomplish because of paucity of chemical leads that are acceptable templates for Medicinal Chemistry investigation...
2016: International Review of Neurobiology
https://www.readbyqxmd.com/read/27238264/functional-role-of-mitochondrial-and-nuclear-bk-channels
#17
B Li, T-M Gao
BK channels are important for the regulation of many cell functions. The significance of plasma membrane BK channels in the control of action potentials, resting membrane potential, and neurotransmitter release is well established; however, the composition and functions of mitochondrial and nuclear BK (nBK) channels are largely unknown. In this chapter, we summarize the recent findings on the subcellular localization, biophysical, and pharmacological properties of mitochondrial and nBK channels and discuss their molecular identity and physiological functions...
2016: International Review of Neurobiology
https://www.readbyqxmd.com/read/27238261/modulation-of-bk-channel-function-by-auxiliary-beta-and-gamma-subunits
#18
Q Li, J Yan
The large-conductance, Ca(2+)- and voltage-activated K(+) (BK) channel is ubiquitously expressed in mammalian tissues and displays diverse biophysical or pharmacological characteristics. This diversity is in part conferred by channel modulation with different regulatory auxiliary subunits. To date, two distinct classes of BK channel auxiliary subunits have been identified: β subunits and γ subunits. Modulation of BK channels by the four auxiliary β (β1-β4) subunits has been well established and intensively investigated over the past two decades...
2016: International Review of Neurobiology
https://www.readbyqxmd.com/read/27165430/different-expression-of-%C3%AE-subunits-of-the-kca1-1-channel-by-invasive-and-non-invasive-human-fibroblast-like-synoviocytes
#19
Zoltán Pethő, Mark R Tanner, Rajeev B Tajhya, Redwan Huq, Teresina Laragione, Gyorgy Panyi, Pércio S Gulko, Christine Beeton
BACKGROUND: Fibroblast-like synoviocytes (FLS) in rheumatoid arthritis (RA-FLS) contribute to joint inflammation and damage characteristic of the disease. RA-FLS express KCa1.1 (BK, Slo1, MaxiK, KCNMA1) as their major plasma membrane potassium channel. Blocking KCa1.1 reduces the invasive phenotype of RA-FLS and attenuates disease severity in animal models of RA. This channel has therefore emerged as a promising therapeutic target in RA. However, the pore-forming α subunit of KCa1.1 is widely distributed in the body, and blocking it induces severe side effects, thus limiting its value as a therapeutic target...
2016: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/27146987/knockout-of-the-bk-%C3%AE-4-subunit-promotes-a-functional-coupling-of-bk-channels-and-ryanodine-receptors-that-mediate-a-fahp-induced-increase-in-excitability
#20
Bin Wang, Vladislav Bugay, Ling Ling, Hui-Hsui Chuang, David B Jaffe, Robert Brenner
BK channels are large-conductance calcium- and voltage-activated potassium channels with diverse properties. Knockout of the accessory BK β4-subunit in hippocampus dentate gyrus granule neurons causes BK channels to change properties from slow-gated type II channels to fast-gated type I channels that sharpen the action potential, increase the fast afterhyperpolarization (fAHP) amplitude, and increase spike frequency. Here we studied the calcium channels that contribute to fast-gated BK channel activation and increased excitability of β4 knockout neurons...
August 1, 2016: Journal of Neurophysiology
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