Open states of nuclear envelope ion channels in cardiac myocytes

1994 ◽  
Vol 138 (1) ◽  
Author(s):  
J.O. Bustamante
Keyword(s):  
Ion Channels ◽  
Nuclear Envelope ◽  
Cardiac Myocytes ◽  
Open States

Nuclear ion channel activity is regulated by actin filaments

1996 ◽  
Vol 270 (5) ◽  
pp. C1532-C1543 ◽  
Author(s):  
A. G. Prat ◽  
H. F. Cantiello
Keyword(s):  
Ion Channels ◽  
Actin Cytoskeleton ◽  
Nuclear Envelope ◽  
Ion Channel ◽  
Actin Filaments ◽  
Actin Binding ◽  
Bathing Solution ◽  
Channel Activity ◽  
Nuclear Ion Channels ◽  
Inside Out

Actin filaments are novel second messengers involved in ion channel regulation. Because cytoskeletal components interact with the nuclear envelope, the actin cytoskeleton may also control nuclear membrane function. In this report, the patch-clamp technique was applied to isolated nuclei from amphibian A6 epithelial cells to assess the role of actin filaments on nuclear ion channel activity under nucleus-attached or -excised conditions. The most prevalent spontaneous nuclear ion channel species, 76% (n = 46), was cation selective and had a maximal single-channel conductance of approximately 420 pS. Nuclear ion channels also displayed multiple subconductance states, including channel activity of 26 pS that was frequently observed. Nuclear ion channel activity on otherwise quiescent patches was induced by either addition of the actin cytoskeleton disrupter cytochalasin D (CD; 5 micrograms/ml, 60%, 3 of 5 patches) or actin (10-1,000 micrograms/ml) to the bathing solution of nucleus-attached patches (59%, 13 of 22 patches). Actin also induced ion channel activity in quiescent excised inside-out patches from the nuclear envelope (80%, 4 of 5 patches). In contrast, addition of bovine serum albumin (10-1,000 micrograms/ml) to the bathing solution of nucleus-attached patches was without effect on nuclear ion channel activity (5 of 5 patches). The monoclonal antibody MAb414, specific for nuclear pore complex proteins, completely prevented either spontaneous or cytosolic actin-induced nuclear ion channels under nucleus-attached conditions (4 of 4 patches) but not intranuclear actin-induced nuclear ion channels under excised inside-out conditions (3 of 3 patches). In nucleus-attached patches, channel activity was readily activated by addition of the G-actin-binding protein deoxyribonuclease I to nucleus-attached patches (56%, 5 of 9 patches) or further addition of the actin-cross-linker filamin in the presence of actin (57%, 4 of 7 patches). The data indicate that dynamic changes in actin filament organization may represent a novel mechanism to control nuclear function.

The large-conductance ion channels in the nuclear envelope of central neurons

2010 ◽  
Vol 460 (6) ◽  
pp. 1045-1050 ◽  
Author(s):  
Olena Fedorenko ◽  
Victor Yarotskyy ◽  
Dmytro Duzhyy ◽  
Sergey Marchenko
Keyword(s):  
Ion Channels ◽  
Nuclear Envelope ◽  
Central Neurons

WHAT CAUSES ION CHANNEL PROTEINS TO FLUCTUATE OPEN AND CLOSED?

1996 ◽  
Vol 07 (04) ◽  
pp. 321-331 ◽  
Author(s):  
LARRY S. LIEBOVITCH ◽  
ANGELO T. TODOROV
Keyword(s):  
Ion Channels ◽  
Patch Clamp ◽  
Ion Channel ◽  
Patch Clamp Technique ◽  
Sodium Potassium ◽  
Random Event ◽  
Channel Protein ◽  
Channel Proteins ◽  
Ion Channel Proteins ◽  
Open States

Ion channels in the cell membrane spontaneously switch from states that are closed to the flow of ions such as sodium, potassium, and chloride to states that are open to the flow of these ions. The durations of times that an individual ion channel protein spends in the closed and open states can be measured by the patch clamp technique. We explore two basic issues about the molecular properties of ion channels: 1) If the switching between the closed and open state is an inherently random event, what does the patch clamp data tell us about the structure or motions in the ion channel protein? 2) Is this switching random?

scholarly journals A valve-like mechanism controls desensitization of functional mammalian isoforms of acid-sensing ion channels

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Yangyu Wu ◽  
Zhuyuan Chen ◽  
Cecilia M Canessa
Keyword(s):  
Steady State ◽  
Ion Channels ◽  
Molecular Mechanism ◽  
Sodium Channels ◽  
Xenopus Oocytes ◽  
Acid Sensing Ion Channels ◽  
Electrophysiological Measurements ◽  
Open States

ASICs are proton-gated sodium channels expressed in neurons. Structures of chicken ASIC1 in three conformations have advanced understanding of proton-mediated gating; however, a molecular mechanism describing desensitization from open and pre-open states (steady-state desensitization or SSD) remains elusive. A distinct feature of the desensitized state is an 180o rotation of residues L415 and N416 in the β11- β12 linker that was proposed to mediate desensitization; whether and how it translates into desensitization has not been explored yet. Using electrophysiological measurements of injected Xenopus oocytes, we show that Q276 in β9 strand works with L415 and N416 to mediate both types of desensitization in ASIC1a, ASIC2a and ASIC3. Q276 functions as a valve that enables or restricts rotation of L415 and N416 to keep the linker compressed, its relaxation lengthens openings and leads to sustained currents. At low proton concentrations, the proposed mechanism working in only one of three subunits of the channel is sufficient to induce SSD.

scholarly journals Haploinsufficiency of Tmem43 in cardiac myocytes activates the DNA damage response pathway leading to a late-onset senescence-associated pro-fibrotic cardiomyopathy

2020 ◽  
Author(s):  
Leila Rouhi ◽  
Sirisha M Cheedipudi ◽  
Suet Nee Chen ◽  
Siyang Fan ◽  
Raffaella Lombardi ◽  
...  
Keyword(s):  
Dna Damage ◽  
Nuclear Envelope ◽  
Cardiac Myocytes ◽  
Myocardial Fibrosis ◽  
Dna Damage Response ◽  
Envelope Protein ◽  
Alternative Methods ◽  
Damage Response ◽  
Age Dependent ◽  
Tp53 Pathway

Abstract Aims Arrhythmogenic cardiomyopathy (ACM) encompasses a genetically heterogeneous group of myocardial diseases whose manifestations are sudden cardiac death, cardiac arrhythmias, heart failure, and in a subset fibro-adipogenic infiltration of the myocardium. Mutations in the TMEM43 gene, encoding transmembrane protein 43 (TMEM43) are known to cause ACM. The purpose of the study was to gain insights into the molecular pathogenesis of ACM caused by TMEM43 haploinsufficiency. Methods and results The Tmem43 gene was specifically deleted in cardiac myocytes by crossing the Myh6-Cre and floxed Tmem43 mice. Myh6-Cre:Tmem43W/F mice showed an age-dependent phenotype characterized by an increased mortality, cardiac dilatation and dysfunction, myocardial fibrosis, adipogenesis, and apoptosis. Sequencing of cardiac myocyte transcripts prior to and after the onset of cardiac phenotype predicted early activation of the TP53 pathway. Increased TP53 activity was associated with increased levels of markers of DNA damage response (DDR), and a subset of senescence-associated secretary phenotype (SASP). Activation of DDR, TP53, SASP, and their selected downstream effectors, including phospho-SMAD2 and phospho-SMAD3 were validated by alternative methods, including immunoblotting. Expression of SASP was associated with epithelial–mesenchymal transition and age-dependent expression of myocardial fibrosis and apoptosis in the Myh6-Cre:Tmem43W/F mice. Conclusion TMEM43 haploinsufficiency is associated with activation of the DDR and the TP53 pathways, which lead to increased expression of SASP and an age-dependent expression of a pro-fibrotic cardiomyopathy. Given that TMEM43 is a nuclear envelope protein and our previous data showing deficiency of another nuclear envelope protein, namely lamin A/C, activates the DDR/TP53 pathway, we surmise that DNA damage is a shared mechanism in the pathogenesis of cardiomyopathies caused by mutations involving nuclear envelope proteins.

Dynamic of Ion Channel Expression at the Plasma Membrane of Cardiomyocytes

2012 ◽  
Vol 92 (3) ◽  
pp. 1317-1358 ◽  
Author(s):  
Elise Balse ◽  
David F. Steele ◽  
Hugues Abriel ◽  
Alain Coulombe ◽  
David Fedida ◽  
...  
Keyword(s):  
Ion Channels ◽  
Ion Channel ◽  
Cardiac Myocytes ◽  
Cardiac Myocyte ◽  
Membrane Lipids ◽  
Current Knowledge ◽  
Small Gtpases ◽  
Molecular Organization ◽  
Cardiac Sarcolemma ◽  
Channel Expression

Cardiac myocytes are characterized by distinct structural and functional entities involved in the generation and transmission of the action potential and the excitation-contraction coupling process. Key to their function is the specific organization of ion channels and transporters to and within distinct membrane domains, which supports the anisotropic propagation of the depolarization wave. This review addresses the current knowledge on the molecular actors regulating the distinct trafficking and targeting mechanisms of ion channels in the highly polarized cardiac myocyte. In addition to ubiquitous mechanisms shared by other excitable cells, cardiac myocytes show unique specialization, illustrated by the molecular organization of myocyte-myocyte contacts, e.g., the intercalated disc and the gap junction. Many factors contribute to the specialization of the cardiac sarcolemma and the functional expression of cardiac ion channels, including various anchoring proteins, motors, small GTPases, membrane lipids, and cholesterol. The discovery of genetic defects in some of these actors, leading to complex cardiac disorders, emphasizes the importance of trafficking and targeting of ion channels to cardiac function. A major challenge in the field is to understand how these and other actors work together in intact myocytes to fine-tune ion channel expression and control cardiac excitability.

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