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bk channel pharmacology

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https://www.readbyqxmd.com/read/29145442/downregulation-of-kcnmb4-expression-and-changes-in-bk-channel-subtype-in-hippocampal-granule-neurons-following-seizure-activity
#1
Luke E Whitmire, Ling Ling, Vladslav Bugay, Chase M Carver, Santosh Timilsina, Hui-Hsiu Chuang, David B Jaffe, Mark S Shapiro, Jose E Cavazos, Robert Brenner
A major challenge is to understand maladaptive changes in ion channels that sets neurons on a course towards epilepsy development. Voltage- and calcium-activated K+ (BK) channels contribute to early spike timing in neurons, and studies indicate that the BK channel plays a pathological role in increasing excitability early after a seizure. Here, we have investigated changes in BK channels and their accessory β4 subunit (KCNMB4) in dentate gyrus (DG) granule neurons of the hippocampus, key neurons that regulate excitability of the hippocampus circuit...
2017: PloS One
https://www.readbyqxmd.com/read/29051185/cgmp-elevating-compounds-and-ischemic-conditioning-provide-cardioprotection-against-ischemia-and-reperfusion-injury-via-cardiomyocyte-specific-bk-channels
#2
Sandra Frankenreiter, Piotr Bednarczyk, Angelina Kniess, Nadja Bork, Julia Straubinger, Piotr Koprowski, Antoni Wrzosek, Eva Mohr, Angela Logan, Michael P Murphy, Meinrad Gawaz, Thomas Krieg, Adam Szewczyk, Viacheslav O Nikolaev, Peter Ruth, Robert Lukowski
Background -The nitric oxide-sensitive guanylyl cyclase (NO-GC)/cyclic guanosine-3',5'-monophosphate (cGMP)/cGMP-dependent protein kinase type I (cGKI)-signaling pathway can afford protection against the ischemia and reperfusion (I/R) injury that occurs during myocardial infarction (MI). Reportedly, voltage and Ca(2+)-activated K(+) channels of the BK-type are stimulated by cGMP/cGKI and recent ex-vivo studies implicated that increased BK activity favors the survival of the myocardium at I/R. It remains unclear, however, whether the molecular events downstream of cGMP involve BK channels present in cardiomyocytes (CMs) or in other cardiac cell types...
October 19, 2017: Circulation
https://www.readbyqxmd.com/read/29050967/role-of-k-channels-in-regulating-spontaneous-activity-in-the-muscularis-mucosae-of-guinea-pig-bladder
#3
Ken Lee, Ayu Isogai, Minori Antoh, Shunichi Kajioka, Masatoshi Eto, Hikaru Hashitani
To explore the roles of various K(+) channels in regulating the spontaneous activity of bladder muscularis mucosae (MM) that is considered to play an important role in maintaining mucosal function. Effects of K(+) channel modulators on electrical and contractile activity in the guinea-pig bladder MM were examined using intracellular microelectrode and isometric tension recording. The MM predominately generated bursting spontaneous action potentials (SAPs) and phasic contractions (SPCs) that were blocked by nifedipine (1µM)...
October 16, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28986465/dendritic-and-axonal-l-type-calcium-channels-cooperate-to-enhance-motoneuron-firing-output-during-drosophila-larval-locomotion
#4
Dimitrios Kadas, Aylin Klein, Niklas Krick, Jason W Worrell, Stefanie Ryglewski, Carsten Duch
Behaviorally adequate neuronal firing patterns are critically dependent on the specific types of ion channel expressed and on their subcellular localization. This study combines in situ electrophysiology with genetic and pharmacological intervention in larval Drosophila melanogaster of both sexes to address localization and function of L-type like calcium channels in motoneurons. We demonstrate that Dmca1D (Cav1 homolog) L-type like calcium channels localize to both, the somatodendritic and the axonal compartment of larval crawling motoneurons...
October 6, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28830977/lack-of-direct-effect-of-adiponectin-on-vascular-smooth-muscle-cell-bkca-channels-or-ca-2-signaling-in-the-regulation-of-small-artery-pressure-induced-constriction
#5
Rachael Baylie, Majid Ahmed, Adrian D Bonev, David C Hill-Eubanks, Thomas J Heppner, Mark T Nelson, Adam S Greenstein
The aim of this study was to investigate mechanisms by which adiponectin influences vascular Ca(2+) signaling, K(+) channel activity and thus contractile tone of small arteries. Vasodilation to adiponectin was studied in mesenteric resistance arteries constricted with intraluminal pressure. Ca(2+) signals were characterized using high speed confocal microscopy of intact arteries. Patch clamp investigated the effect of adiponectin on individual VSMC potassium (K(+)) channel currents. Adiponectin dilated arteries constricted with pressure-induced tone by approximately 5% and the induced vasodilation was only transient...
August 2017: Physiological Reports
https://www.readbyqxmd.com/read/28818302/mitochondrial-ca-2-activated-k-channels-and-their-role-in-cell-life-and-death-pathways
#6
REVIEW
Inge E Krabbendam, Birgit Honrath, Carsten Culmsee, Amalia M Dolga
Ca(2+)-activated K(+) channels (KCa) are expressed at the plasma membrane and in cellular organelles. Expression of all KCa channel subtypes (BK, IK and SK) has been detected at the inner mitochondrial membrane of several cell types. Primary functions of these mitochondrial KCa channels include the regulation of mitochondrial ROS production, maintenance of the mitochondrial membrane potential and preservation of mitochondrial calcium homeostasis. These channels are therefore thought to contribute to cellular protection against oxidative stress through mitochondrial mechanisms of preconditioning...
July 22, 2017: Cell Calcium
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
#7
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
#8
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...
October 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28600454/the-slo-w-path-to-identifying-the-mitochondrial-channels-responsible-for-ischemic-protection
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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...
January 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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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