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bk channel pore

Rajeev B Tajhya, Xueyou Hu, Mark R Tanner, Redwan Huq, Natee Kongchan, Joel R Neilson, George G Rodney, Frank T Horrigan, Lubov T Timchenko, Christine Beeton
Myoblasts are mononucleated precursors of myofibers; they persist in mature skeletal muscles for growth and regeneration post injury. During myotonic dystrophy type 1 (DM1), a complex autosomal-dominant neuromuscular disease, the differentiation of skeletal myoblasts into functional myotubes is impaired, resulting in muscle wasting and weakness. The mechanisms leading to this altered differentiation are not fully understood. Here, we demonstrate that the calcium- and voltage-dependent potassium channel, KCa1...
October 20, 2016: Cell Death & Disease
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...
October 17, 2016: Naunyn-Schmiedeberg's Archives of Pharmacology
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 four 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 three sites in the extracellular loop of β2 subunit are N-glycosylated (N-X-T/S at N88, N96 and N119)...
October 3, 2016: Channels
Jiusheng Yan, Qin Li, Richard W Aldrich
Ion channels regulate ion flow by opening and closing their pore gates. K(+) channels commonly possess two pore gates, one at the intracellular end for fast channel activation/deactivation and the other at the selectivity filter for slow C-type inactivation/recovery. The large-conductance calcium-activated potassium (BK) channel lacks a classic intracellular bundle-crossing activation gate and normally show no C-type inactivation. We hypothesized that the BK channel's activation gate may spatially overlap or coexist with the C-type inactivation gate at or near the selectivity filter...
June 21, 2016: Proceedings of the National Academy of Sciences of the United States of America
T Hoshi, S H Heinemann
Voltage- and Ca(2+)-activated K(+) channels of big conductance (BK channels) are abundantly found in various organs and their relevance for smooth muscle tone and neuronal signaling is well documented. Dysfunction of BK channels is implicated in an array of human diseases involving many organs including the nervous, pulmonary, cardiovascular, renal, and urinary systems. In humans a single gene (KCNMA1) encodes the pore-forming α subunit (Slo1) of BK channels, but the channel properties are variable because of alternative splicing, tissue- and subcellular-specific auxiliary subunits (β, γ), posttranslational modifications, and a multitude of endogenous signaling molecules directly affecting the channel function...
2016: International Review of Neurobiology
M J Shipston, L Tian
Large conductance calcium- and voltage-activated potassium (BK) channels are ubiquitously expressed and play an important role in the regulation of an eclectic array of physiological processes. Their diverse functional role requires channels with a wide variety of properties even though the pore-forming α-subunit is encoded by a single gene, KCNMA1. To achieve this, BK channels exploit some of the most fundamental posttranscriptional and posttranslational mechanisms that allow proteomic diversity to be generated from a single gene...
2016: International Review of Neurobiology
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
Qin Li, Xin Guan, Karen Yen, Jiyuan Zhang, Jiusheng Yan
The large-conductance, calcium-activated potassium (BK) channels consist of the pore-forming, voltage- and Ca(2+)-sensing α subunits (BKα) and the tissue-specific auxiliary β and γ subunits. The BK channel γ1 subunit is a leucine-rich repeat (LRR)-containing membrane protein that potently facilitates BK channel activation in many tissues and cell types through a vast shift in the voltage dependence of channel activation by ∼140 mV in the hyperpolarizing direction. In this study, we found that the single transmembrane (TM) segment together with its flanking charged residues is sufficient to fully modulate BK channels upon its transplantation into the structurally unrelated β1 subunit...
April 2016: Journal of General Physiology
Marilena Griguoli, Martina Sgritta, Enrico Cherubini
BK channels are large conductance potassium channels characterized by four pore-forming α subunits, often co-assembled with auxiliary β and γ subunits to regulate Ca(2+) sensitivity, voltage dependence and gating properties. Abundantly expressed in the CNS, they have the peculiar characteristic of being activated by both voltage and intracellular calcium rise. The increase in intracellular calcium via voltage-dependent calcium channels (Cav ) during spiking triggers conformational changes and BK channel opening...
July 1, 2016: Journal of Physiology
Hans Moldenhauer, Ignacio Díaz-Franulic, Fernando González-Nilo, David Naranjo
Reconciling protein functional data with crystal structure is arduous because rare conformations or crystallization artifacts occur. Here we present a tool to validate the dimensions of open pore structures of potassium-selective ion channels. We used freely available algorithms to calculate the molecular contour of the pore to determine the effective internal pore radius (r(E)) in several K-channel crystal structures. r(E) was operationally defined as the radius of the biggest sphere able to enter the pore from the cytosolic side...
2016: Scientific Reports
Rolando Carrisoza-Gaytan, Marcelo D Carattino, Thomas R Kleyman, Lisa M Satlin
Flow-induced K secretion (FIKS) in the aldosterone-sensitive distal nephron (ASDN) is mediated by large-conductance, Ca(2+)/stretch-activated BK channels composed of pore-forming α-subunits (BKα) and accessory β-subunits. This channel also plays a critical role in the renal adaptation to dietary K loading. Within the ASDN, the cortical collecting duct (CCD) is a major site for the final renal regulation of K homeostasis. Principal cells in the ASDN possess a single apical cilium whereas the surfaces of adjacent intercalated cells, devoid of cilia, are decorated with abundant microvilli and microplicae...
February 15, 2016: American Journal of Physiology. Cell Physiology
E L Belyaeva
ATP-producing cell organelles, mitochondria, are the primary target for heavy metals which are major environmental pollutants and cause various pathological conditions and diseases. It has been established that the mechanism of toxic action of heavy metals, includes changes in the intracellular production of reactive oxygen species and mitochondrial dysfunction mediated by disturbances of the respiratory chain and by activation of Ca2+-dependent nonselective pore of the inner mitochondrial membrane. The role of other ion channels, in particular such selective potassium channels as Ca2+ activated large-conductance potassium channels, BK(Ca), considered to be <protective> for a cell, is practically not investigated...
July 2015: Zhurnal Evoliutsionnoĭ Biokhimii i Fiziologii
Betsir G Zemen, Michael H Lai, Joshua P Whitt, Zulqarnain Khan, Guiling Zhao, Andrea L Meredith
BK large conductance calcium-activated K(+) channels (KC a1.1) are expressed widely across many tissues, contributing to systemic regulation of cardiovascular, neurological, and other specialized physiological functions. The pore-forming α subunit is encoded by the Kcnma1 gene, originally named mSlo1 in mouse and slowpoke in Drosophila. Global deletion in mouse (Kcnma1(-/-)) produces a plethora of defects in neuron and muscle excitability, as well as other phenotypes related to channel function in nonexcitable cells...
November 2015: Physiological Reports
M A Hollywood
BACKGROUND: The Conway Review Lecture is held annually by the Royal Academy of Medicine in Ireland Biomedical Sciences Section, to remember the life and scientific work of a world class Irish scientist, Professor Edward J Conway. AIMS: This years lecture will focus on large conductance Ca2+ activated K+ (BK) channels and aims to describe how a combination of techniques can be used to unravel drug effects on ion channels at a molecular level. METHODS: Experiments were performed using a range of techniques including patch clamp electrophysiology, mutagenesis, structural biology and mathematical modeling...
February 2016: Irish Journal of Medical Science
L N Maslov, N V Naryzhnaya, J-M Pei, Y Zhang, H Wang, I J Khaliulin, Yu B Lishmanov
It is well known that cardiovascular disease and in particular acute myocardial infarction are a major cause of death among working-age population in Russia. Some of the patients die after successful recanalization of the infarct-related coronary artery as a result of ischemic and reperfusion injury of the heart. It is obvious that there is an urgent need to develop new approaches to prevention reoxygenation heart damages. In this regard the study of adaptive phenomenon postconditioning is of particular interest...
June 2015: Rossiĭskii Fiziologicheskiĭ Zhurnal Imeni I.M. Sechenova
Christopher P Pratt, Jianjun He, Yi Wang, Alison L Barth, Marcel P Bruchez
The regulation of surface levels of protein is critical for proper cell function and influences properties including cell adhesion, ion channel contributions to current flux, and the sensitivity of surface receptors to ligands. Here we demonstrate a two-color labeling system in live cells using a single fluorogen activating peptide (FAP) based fusion tag, which enables the rapid and simultaneous quantification of surface and internal proteins. In the nervous system, BK channels can regulate neural excitability and neurotransmitter release, and the surface trafficking of BK channels can be modulated by signaling cascades and assembly with accessory proteins...
September 16, 2015: Bioconjugate Chemistry
Ignacio Díaz-Franulic, Romina V Sepúlveda, Nieves Navarro-Quezada, Fernando González-Nilo, David Naranjo
K channels mediate the selective passage of K(+) across the plasma membrane by means of intimate interactions with ions at the pore selectivity filter located near the external face. Despite high conservation of the selectivity filter, the K(+) transport properties of different K channels vary widely, with the unitary conductance spanning a range of over two orders of magnitude. Mutation of Pro475, a residue located at the cytoplasmic entrance of the pore of the small-intermediate conductance K channel Shaker (Pro475Asp (P475D) or Pro475Gln (P475Q)), increases Shaker's reported ∼ 20-pS conductance by approximately six- and approximately threefold, respectively, without any detectable effect on its selectivity...
August 2015: Journal of General Physiology
Maria Derksen, Christian Vorwerk, Detlef Siemen
The permeability transition pore (PTP) of inner mitochondrial membranes is a large conductance pathway for ions up to 1500 Da which opening is responsible for ion equilibration and loss of membrane potential in apoptosis and thus in several neurodegenerative diseases. The PTP can be regulated by the Ca(2+)-activated mitochondrial K channel (BK). Calpains are Ca(2+)-activated cystein proteases; calpeptin is an inhibitor of calpains. We wondered whether calpain or calpeptin can modulate activity of PTP or BK...
May 2016: Protoplasma
Joseph R Stimers, Li Song, Nancy J Rusch, Sung W Rhee
Long QT syndrome is characterized by a prolongation of the interval between the Q wave and the T wave on the electrocardiogram. This abnormality reflects a prolongation of the ventricular action potential caused by a number of genetic mutations or a variety of drugs. Since effective treatments are unavailable, we explored the possibility of using cardiac expression of the large-conductance, Ca2+-activated K+ (BK) channel to shorten action potential duration (APD). We hypothesized that expression of the pore-forming α subunit of human BK channels (hBKα) in HL-1 cells would shorten action potential duration in this mouse atrial cell line...
2015: PloS One
Qin Li, Fei Fan, Ha Rim Kwak, Jiusheng Yan
Large conductance Ca(2+)- and voltage-activated potassium (BK) channels are comprised of pore-forming α subunits and various regulatory auxiliary subunits. The BK channel auxiliary γ (BKγ) subunits are a newly identified class of proteins containing an extracellular leucine-rich repeat domain (LRRD), a single transmembrane (TM) segment, and a short cytoplasmic C-terminal tail (C-tail). Although each of the four BKγ proteins shifts the voltage dependence of BK channel activation in a hyperpolarizing direction, they show markedly different efficacies, mediating shifts over a range of 15-145 mV...
June 2015: Journal of General Physiology
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