Alternative Splicing Of Large Conductance Calcium And Voltage Activated Potassium Bk Channels
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Alternative Splicing Of Large Conductance Calcium And Voltage Activated Potassium Bk Channels
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Author : Stephen Hsiao-Feng Macdonald
language : en
Publisher:
Release Date : 2006
Alternative Splicing Of Large Conductance Calcium And Voltage Activated Potassium Bk Channels written by Stephen Hsiao-Feng Macdonald and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2006 with categories.
Alternate Exons In Caenorhabditis Elegans Slo 1 Diversify Bk Channel Calcium Dependence
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Author : Brandon Eugene Johnson
language : en
Publisher: Stanford University
Release Date : 2010
Alternate Exons In Caenorhabditis Elegans Slo 1 Diversify Bk Channel Calcium Dependence written by Brandon Eugene Johnson and has been published by Stanford University this book supported file pdf, txt, epub, kindle and other format this book has been release on 2010 with categories.
Ion channels coordinate the movement of ions across biological membranes in response to a diversity of cellular signals to regulate most if not all aspects of physiology. The large-conductance Ca2+- and voltage-activated potassium (BK) channel is widely expressed across tissues and functions to repolarize action potentials, regulate smooth muscle tone and endocrine function, and tune auditory hair cells. In all tissues, BK channels provide a functional link between cytosolic Ca2+ and membrane excitation. Extensive alternate splicing of the slo-1 gene, encoding the BK channel, significantly diversifies channel function. We identified all twelve predicted BK channel splice variants expressed by the nematode Caenorhabditis elegans, and measured the Ca2+ and voltage dependence for each. Alternate exons encode portions of two regions of the cytoplasmic tail: the RCK domain, important for Ca2+ coordination, and an unstructured region, termed the C-linker. Using the patch clamp technique, we determined that alternate splicing across multiple sites diversifies activation kinetics and Ca2+ sensitivity by manipulating the functional interaction between the RCK domain and C-linker. We recovered two slo-1 alleles (pg34 and pg52) that contain point-mutations near an alternative splice site in the C-linker from a mutant screen. Using real-time PCR, we determined that both mutations change slo-1 splice variant expression profiles. The pg34 mutation encodes an A698T substitution, and the pg52 mutation is located in an intron. When heterologously expressed, the A698T mutation changes BK channel Ca2+ sensitivity in specific splice variant backgrounds by disrupting the functional connection between the C-linker and the RCK domain. Using in vivo electrophysiology, we determined that the pg34 mutation reduces but does not abolish BK channel function in C. elegans neurons. These results suggest that alternate splicing of slo-1 modulates the functional connection between the RCK domain and the C-linker of the BK channel to establish a proper balance between intracellular Ca2+ and membrane excitation in a variety of cell type and physiological conditions.
Big On Bk
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Author :
language : en
Publisher: Academic Press
Release Date : 2016-05-26
Big On Bk written by and has been published by Academic Press this book supported file pdf, txt, epub, kindle and other format this book has been release on 2016-05-26 with Science categories.
Big on Bk: Current Insights into the Function of Large Conductance Voltage- and Ca2+- Activated K+ Channels at the Molecular, Cellular and Systemic Levels, a volume in the International Review of Neurobiology series, is a comprehensive overview of the state-of-the-art research into this area. It reviews current knowledge and understanding, and also provides a starting point for researchers and practitioners entering the field. The latest volume in the International Review of Neurobiology series Provides a broad coverage of subject matter at the molecular, cellular and systemic levels Presents an ideal resource for researchers and practitioners, and those just entering the field
Alternate Exons In Caenorhabditis Elegans Slo 1 Diversify Bk Channel Calcium Dependence
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Author : Brandon Eugene Johnson
language : en
Publisher:
Release Date : 2010
Alternate Exons In Caenorhabditis Elegans Slo 1 Diversify Bk Channel Calcium Dependence written by Brandon Eugene Johnson and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2010 with categories.
Ion channels coordinate the movement of ions across biological membranes in response to a diversity of cellular signals to regulate most if not all aspects of physiology. The large-conductance Ca2+- and voltage-activated potassium (BK) channel is widely expressed across tissues and functions to repolarize action potentials, regulate smooth muscle tone and endocrine function, and tune auditory hair cells. In all tissues, BK channels provide a functional link between cytosolic Ca2+ and membrane excitation. Extensive alternate splicing of the slo-1 gene, encoding the BK channel, significantly diversifies channel function. We identified all twelve predicted BK channel splice variants expressed by the nematode Caenorhabditis elegans, and measured the Ca2+ and voltage dependence for each. Alternate exons encode portions of two regions of the cytoplasmic tail: the RCK domain, important for Ca2+ coordination, and an unstructured region, termed the C-linker. Using the patch clamp technique, we determined that alternate splicing across multiple sites diversifies activation kinetics and Ca2+ sensitivity by manipulating the functional interaction between the RCK domain and C-linker. We recovered two slo-1 alleles (pg34 and pg52) that contain point-mutations near an alternative splice site in the C-linker from a mutant screen. Using real-time PCR, we determined that both mutations change slo-1 splice variant expression profiles. The pg34 mutation encodes an A698T substitution, and the pg52 mutation is located in an intron. When heterologously expressed, the A698T mutation changes BK channel Ca2+ sensitivity in specific splice variant backgrounds by disrupting the functional connection between the C-linker and the RCK domain. Using in vivo electrophysiology, we determined that the pg34 mutation reduces but does not abolish BK channel function in C. elegans neurons. These results suggest that alternate splicing of slo-1 modulates the functional connection between the RCK domain and the C-linker of the BK channel to establish a proper balance between intracellular Ca2+ and membrane excitation in a variety of cell type and physiological conditions.
Regulation Of Cloned Large Conductance Calcium Activated Potassium Bk Channels By Reversible Protein Phosphorylation
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Author : Martin Sinclair Lyle Hammond
language : en
Publisher:
Release Date : 2000
Regulation Of Cloned Large Conductance Calcium Activated Potassium Bk Channels By Reversible Protein Phosphorylation written by Martin Sinclair Lyle Hammond and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2000 with categories.
Potassium Channels Advances In Research And Application 2011 Edition
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Author :
language : en
Publisher: ScholarlyEditions
Release Date : 2012-01-09
Potassium Channels Advances In Research And Application 2011 Edition written by and has been published by ScholarlyEditions this book supported file pdf, txt, epub, kindle and other format this book has been release on 2012-01-09 with Science categories.
Potassium Channels: Advances in Research and Application: 2011 Edition is a ScholarlyBrief™ that delivers timely, authoritative, comprehensive, and specialized information about Potassium Channels in a concise format. The editors have built Potassium Channels: Advances in Research and Application: 2011 Edition on the vast information databases of ScholarlyNews.™ You can expect the information about Potassium Channels in this eBook to be deeper than what you can access anywhere else, as well as consistently reliable, authoritative, informed, and relevant. The content of Potassium Channels: Advances in Research and Application: 2011 Edition has been produced by the world’s leading scientists, engineers, analysts, research institutions, and companies. All of the content is from peer-reviewed sources, and all of it is written, assembled, and edited by the editors at ScholarlyEditions™ and available exclusively from us. You now have a source you can cite with authority, confidence, and credibility. More information is available at http://www.ScholarlyEditions.com/.
Regulation Of A Large Conductance Calcium Activated Potassium Bk Channel By J Proteins
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Author : Eva Ahrendt
language : en
Publisher:
Release Date : 2012
Regulation Of A Large Conductance Calcium Activated Potassium Bk Channel By J Proteins written by Eva Ahrendt and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2012 with categories.
Palmitoylation Of Large Conductance Voltage And Calcium Dependent Potassium Bk Channels
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Author : Danlei Bi
language : en
Publisher:
Release Date : 2014
Palmitoylation Of Large Conductance Voltage And Calcium Dependent Potassium Bk Channels written by Danlei Bi and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2014 with categories.
Voltage And Calcium Activated Potassium Channel Voltage Sensor Remodeling By Modulatory Beta Subunits And Heme
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Author : Saemi Park
language : en
Publisher:
Release Date : 2014
Voltage And Calcium Activated Potassium Channel Voltage Sensor Remodeling By Modulatory Beta Subunits And Heme written by Saemi Park and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2014 with categories.
Large-conductance voltage- and Ca2+-activated K+ channels (BK) have a broad distribution of expression in mammalian cells. BK channels are activated by the membrane depolarization and elevation of intracellular free calcium. When the channel is activated, it allows an increase in potassium permeability, which hyperpolarizes the membrane electrical potential, suppressing cellular excitability. This membrane hyperpolarization decreases the activity of voltage-gated channels, including Ca2+ channels: the latter confers a significant role of BK channels in the internal calcium homeostasis. BK channels are involved in various fundamental physiological processes including the control of blood pressure and neuronal excitability. The BK channel is a homotetramer consisting of four pore-forming alpha subunits, which encode for seven membrane-spanning domains (S0-S6) and two large intracellular domains, RCK1 and RCK2. S0-S4 segments are known as the voltage sensing domain (VSD); S5 and S6 form the pore region and are involved in ion selectivity, while the RCK domains assemble into the ligand-sensing Gating Ring superstructure. In different tissues, the activity of BK alpha subunits is tuned by their association with modulatory beta subunits, beta1-4. The first project investigated the voltage-dependent structural rearrangements of the human BK channel in the presence of beta1 subunit. The data showed that the association of beta 1 remodeled the VSD movements. It is postulated that the association with beta1 destabilizes the active conformation of the voltage sensor in the absence of Ca2+, thus producing an overall right shift in its voltage dependence. BK channels are also modulated by small cytosolic ligands such as heme. The RCK1-RCK2 linker possesses a conserved heme regulation motif (HRM) and exhibited structural homology to cytochrome C (CytC), a hemoprotein. In particular, BK Methionine-691 aligned with M80 of the CytC, the second axial ligand (outside the HRM) to the heme iron. The goal of the second project aimed to understand the role of M691 in the BK regulation by heme. The mutation M691A dramatically diminished the inhibition of BK channel opening by heme (100 nM) compared with the wild-type BK, suggesting that M691 is critical for heme binding.
Brain Tumors
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Author : Amit Agrawal
language : en
Publisher: BoD – Books on Demand
Release Date : 2022-04-20
Brain Tumors written by Amit Agrawal and has been published by BoD – Books on Demand this book supported file pdf, txt, epub, kindle and other format this book has been release on 2022-04-20 with Medical categories.
Brain tumors comprise a spectrum of histological patterns. Their presentation and management depend on their location, size, and grade of lesions. This book is a collection of high-quality research work from global experts on brain tumors, including meningiomas, and their treatment.