scholarly journals Molecular Tools for Targeted Control of Nerve Cell Electrical Activity. Part I

Acta Naturae ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 52-64
Author(s):  
Danila V. Kolesov ◽  
Elena L. Sokolinskaya ◽  
Konstantin A. Lukyanov ◽  
Alexey M. Bogdanov
Keyword(s):  
Electrical Activity ◽  
Basic Element ◽  
Effector Proteins ◽  
Molecular Tools ◽  
Excitable Cells ◽  
Neuronal Systems ◽  
Multicellular Organisms ◽  
External Stimuli ◽  
Reductionist Approach ◽  
Minimally Invasive Methods

In modern life sciences, the issue of a specific, exogenously directed manipulation of a cells biochemistry is a highly topical one. In the case of electrically excitable cells, the aim of the manipulation is to control the cells electrical activity, with the result being either excitation with subsequent generation of an action potential or inhibition and suppression of the excitatory currents. The techniques of electrical activity stimulation are of particular significance in tackling the most challenging basic problem: figuring out how the nervous system of higher multicellular organisms functions. At this juncture, when neuroscience is gradually abandoning the reductionist approach in favor of the direct investigation of complex neuronal systems, minimally invasive methods for brain tissue stimulation are becoming the basic element in the toolbox of those involved in the field. In this review, we describe three approaches that are based on the delivery of exogenous, genetically encoded molecules sensitive to external stimuli into the nervous tissue. These approaches include optogenetics (Part I) as well as chemogenetics and thermogenetics (Part II), which are significantly different not only in the nature of the stimuli and structure of the appropriate effector proteins, but also in the details of experimental applications. The latter circumstance is an indication that these are rather complementary than competing techniques.

scholarly journals A Software Architecture to Mimic a Ventricular Tachycardia in Intact Murine Hearts by Means of an All-Optical Platform

2019 ◽  
Vol 2 (1) ◽  
pp. 7 ◽  
Author(s):  
Francesco Giardini ◽  
Valentina Biasci ◽  
Marina Scardigli ◽  
Francesco S. Pavone ◽  
Gil Bub ◽  
...  
Keyword(s):  
Ventricular Tachycardia ◽  
Electrical Activity ◽  
Real Time ◽  
Temporal Resolution ◽  
Technical Note ◽  
High Temporal Resolution ◽  
Excitable Cells ◽  
New Approach ◽  
Cardiac Electrical Activity ◽  
All Optical

Optogenetics is an emerging method that uses light to manipulate electrical activity in excitable cells exploiting the interaction between light and light-sensitive depolarizing ion channels, such as channelrhodopsin-2 (ChR2). Initially used in the neuroscience, it has been adopted in cardiac research where the expression of ChR2 in cardiac preparations allows optical pacing, resynchronization and defibrillation. Recently, optogenetics has been leveraged to manipulate cardiac electrical activity in the intact heart in real-time. This new approach was applied to simulate a re-entrant circuit across the ventricle. In this technical note, we describe the development and the implementation of a new software package for real-time optogenetic intervention. The package consists of a single LabVIEW program that simultaneously captures images at very high frame rates and delivers precisely timed optogenetic stimuli based on the content of the images. The software implementation guarantees closed-loop optical manipulation at high temporal resolution by processing the raw data in workstation memory. We demonstrate that this strategy allows the simulation of a ventricular tachycardia with high stability and with a negligible loss of data with a temporal resolution of up to 1 ms.

scholarly journals Effect of acute noise trauma on the gene expression profile of the hippocampus

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Chang Ho Lee ◽  
Kyung Woon Kim ◽  
So Min Lee ◽  
So Young Kim
Keyword(s):  
Gene Expression ◽  
Noise Exposure ◽  
Control Group ◽  
Sprague Dawley ◽  
Qrt Pcr ◽  
Neuronal Systems ◽  
Immune Related Genes ◽  
Pathway Analyses ◽  
Upregulated Genes ◽  
External Stimuli

Abstract Background This study aimed to investigate the changes in the expression of hippocampal genes upon acute noise exposure. Methods Three-week-old Sprague–Dawley rats were assigned to control (n = 15) and noise (n = 15) groups. White noise (2–20 kHz, 115 dB sound pressure level [SPL]) was delivered for 4 h per day for 3 days to the noise group. All rats were sacrificed on the last day of noise exposure, and gene expression in the hippocampus was analyzed using a microarray. Pathway analyses were conducted for genes that showed differential expression ≥ 1.5-fold and P ≤ 0.05 compared to the control group. The genes included in the putative pathways were measured using quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Results Thirty-eight upregulated genes and 81 downregulated genes were identified. The pathway analyses revealed that upregulated genes were involved in the cellular responses to external stimuli and immune system pathways. qRT-PCR confirmed the upregulation of the involved genes. The downregulated genes were involved in neuronal systems and synapse-related pathways, and qRT-PCR confirmed the downregulation of the involved genes. Conclusions Acute noise exposure upregulated the expression of immune-related genes and downregulated the expression of neurotransmission-related genes in the hippocampus.

Reversible Photothermal Modulation of Electrical Activity of Excitable Cells using Polydopamine Nanoparticles

2021 ◽  
pp. 2008809
Author(s):  
Hamed Gholami Derami ◽  
Prashant Gupta ◽  
Kuo‐Chan Weng ◽  
Anushree Seth ◽  
Rohit Gupta ◽  
...  
Keyword(s):  
Electrical Activity ◽  
Excitable Cells

scholarly journals Logical complexity of Bcl-2 family proteins function in the intrinsic apoptosis

2019 ◽  
Vol 147 (1-2) ◽  
pp. 99-104
Author(s):  
Marian Adamkov
Keyword(s):  
Effector Proteins ◽  
Mitochondrial Outer Membrane ◽  
Intermembrane Space ◽  
Intrinsic Apoptosis ◽  
Mitochondrial Outer Membrane Permeabilization ◽  
Molecular Features ◽  
Mitochondrial Intermembrane Space ◽  
Cellular Pathways ◽  
Apoptotic Pathways ◽  
Multicellular Organisms

Apoptosis (type of programmed cell death) is an active process of cellular self-destruction in multicellular organisms. It is characterized by distinctive histomorphological, biochemical, and molecular features. Multiple cellular pathways trigger apoptosis, two of them are the best known: intrinsic and extrinsic. Multiple cellular signals and interactions can influence the course of apoptotic pathways. Bcl-2 family proteins play a key role in regulatory mechanisms of intrinsic apoptosis. Mitochondrial outer membrane permeabilization (MOMP) is an essential step for intrinsic apoptosis that is controlled by pro-apoptotic and anti-apoptotic members of Bcl-2 protein family. Pro-apoptotic effector proteins Bax and Bak represent the only Bcl-2 proteins inducing formation of MOMP, whose pores facilitate the subsequent releasing of several pro-apoptotic proteins from mitochondrial intermembrane space into cytosol. These proteins initiate a caspase cascade, resulting in rapid elimination of the doomed cells.

scholarly journals From Local to Global Modeling for Characterizing Calcium Dynamics and Their Effects on Electrical Activity and Exocytosis in Excitable Cells

2019 ◽  
Vol 20 (23) ◽  
pp. 6057
Author(s):  
Francesco Montefusco ◽  
Morten Pedersen
Keyword(s):  
Electrical Activity ◽  
Pituitary Cells ◽  
Calcium Dynamics ◽  
Excitable Cells ◽  
Global Modeling ◽  
Local Effects ◽  
Complex Interactions ◽  
Electrophysiological Responses ◽  
Global Coupling ◽  
Ca2 Channels

Electrical activity in neurons and other excitable cells is a result of complex interactions between the system of ion channels, involving both global coupling (e.g., via voltage or bulk cytosolic Ca2+ concentration) of the channels, and local coupling in ion channel complexes (e.g., via local Ca2+ concentration surrounding Ca2+ channels (CaVs), the so-called Ca2+ nanodomains). We recently devised a model of large-conductance BKCa potassium currents, and hence BKCa–CaV complexes controlled locally by CaVs via Ca2+ nanodomains. We showed how different CaV types and BKCa–CaV stoichiometries affect whole-cell electrical behavior. Ca2+ nanodomains are also important for triggering exocytosis of hormone-containing granules, and in this regard, we implemented a strategy to characterize the local interactions between granules and CaVs. In this study, we coupled electrical and exocytosis models respecting the local effects via Ca2+ nanodomains. By simulating scenarios with BKCa–CaV complexes with different stoichiometries in pituitary cells, we achieved two main electrophysiological responses (continuous spiking or bursting) and investigated their effects on the downstream exocytosis process. By varying the number and distance of CaVs coupled with the granules, we found that bursting promotes exocytosis with faster rates than spiking. However, by normalizing to Ca2+ influx, we found that bursting is only slightly more efficient than spiking when CaVs are far away from granules, whereas no difference in efficiency between bursting and spiking is observed with close granule-CaV coupling.

scholarly journals How to Take Autophagy and Endocytosis Up a Notch

2014 ◽  
Vol 2014 ◽  
pp. 1-12 ◽  
Author(s):  
Julia M. I. Barth ◽  
Katja Köhler
Keyword(s):  
Notch Signaling ◽  
Signaling Pathways ◽  
Signaling Pathway ◽  
Notch Signaling Pathway ◽  
Effector Proteins ◽  
Common Features ◽  
The Common ◽  
Multicellular Organisms

The interconnection of the endocytic and autophagosomal trafficking routes has been recognized more than two decades ago with both pathways using a set of identical effector proteins and sharing the same ultimate lysosomal destination. More recent data sheds light onto how other pathways are intertwined into this network, and how degradation via the endosomal/autophagosomal system may affect signaling pathways in multicellular organisms. Here, we briefly review the common features of autophagy and endocytosis and discuss how other players enter this mix with particular respect to the Notch signaling pathway.

Electrophysiology of functional subsidiary pacemakers in canine right atrium

1985 ◽  
Vol 249 (3) ◽  
pp. H594-H603 ◽  
Author(s):  
G. J. Rozanski ◽  
S. L. Lipsius
Keyword(s):  
Electrical Activity ◽  
Right Atrium ◽  
Action Potentials ◽  
Triggered Activity ◽  
Diastolic Depolarization ◽  
Cycle Lengths ◽  
Lower Maximum ◽  
Exit Block ◽  
External Stimuli

Glass microelectrodes were used to study the electrical activity of the subsidiary atrial pacemaker (SAP) cells that maintain atrial excitation after suppression of the sinoatrial node. Tissues with documented SAP activity were isolated from the canine inferior right atrium and superfused in vitro with Tyrode solution containing norepinephrine (NE, 10(-8)-10(-7) M). SAP action potentials exhibited prominent diastolic depolarization and a significantly lower maximum diastolic potential, take-off potential, overshoot, rate of rise, and amplitude than typical atrial muscle. Withdrawal of NE completely blocked SAP propagation, although SAP automaticity continued at a slower rate. Acetylcholine (ACh, 5 X 10(-8) M) usually produced complete exit block and decreased spontaneous rate. Higher concentrations of ACh (10(-6) M) elicited a prominent hyperpolarization (19.2 +/- 6.6 mV), completely suppressing SAP automaticity. In quiescent preparations exposed to NE greater than or equal to 10(-7) M, external stimuli at short cycle lengths (less than 1,000 ms) elicited action potentials with delayed afterdepolarizations, which frequently caused nondriven repetitive activity. This triggered activity was inhibited by verapamil or withdrawal of NE. These studies identify and characterize the electrical activity of functional subsidiary pacemakers located in a specific region of the inferior right atrium. In addition, fibers within this region display triggered activity. Spontaneous activity generated by fibers within the SAP region may cause atrial dysrhythmias.

scholarly journals Smart Supra- and Macro-Molecular Tools for Biomedical Applications

Materials ◽  
2020 ◽  
Vol 13 (15) ◽  
pp. 3343
Author(s):  
Mariana Pinteala ◽  
Marc J. M. Abadie ◽  
Radu D. Rusu
Keyword(s):  
Drug Delivery ◽  
Biomedical Applications ◽  
Viral Vectors ◽  
Polymeric Materials ◽  
External Source ◽  
Stimuli Responsive ◽  
Molecular Tools ◽  
Field Function ◽  
Materials Used ◽  
External Stimuli

Stimuli-responsive, “smart” polymeric materials used in the biomedical field function in a bio-mimicking manner by providing a non-linear response to triggers coming from a physiological microenvironment or other external source. They are built based on various chemical, physical, and biological tools that enable pH and/or temperature-stimulated changes in structural or physicochemical attributes, like shape, volume, solubility, supramolecular arrangement, and others. This review touches on some particular developments on the topic of stimuli-sensitive molecular tools for biomedical applications. Design and mechanistic details are provided concerning the smart synthetic instruments that are employed to prepare supra- and macro-molecular architectures with specific responses to external stimuli. Five major themes are approached: (i) temperature- and pH-responsive systems for controlled drug delivery; (ii) glycodynameric hydrogels for drug delivery; (iii) polymeric non-viral vectors for gene delivery; (iv) metallic nanoconjugates for biomedical applications; and, (v) smart organic tools for biomedical imaging.

scholarly journals Store Operated Calcium Entry in Cell Migration and Cancer Metastasis

Cells ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 1246
Author(s):  
Ayat S. Hammad ◽  
Khaled Machaca
Keyword(s):  
Cell Migration ◽  
Cancer Metastasis ◽  
Cell Movement ◽  
Excitable Cells ◽  
Cellular Events ◽  
Store Operated Calcium Entry ◽  
Directional Cell Migration ◽  
Multicellular Organisms ◽  
Migrating Cells

Ca2+ signaling is ubiquitous in eukaryotic cells and modulates many cellular events including cell migration. Directional cell migration requires the polarization of both signaling and structural elements. This polarization is reflected in various Ca2+ signaling pathways that impinge on cell movement. In particular, store-operated Ca2+ entry (SOCE) plays important roles in regulating cell movement at both the front and rear of migrating cells. SOCE represents a predominant Ca2+ influx pathway in non-excitable cells, which are the primary migrating cells in multicellular organisms. In this review, we summarize the role of Ca2+ signaling in cell migration with a focus on SOCE and its diverse functions in migrating cells and cancer metastasis. SOCE has been implicated in regulating focal adhesion turnover in a polarized fashion and the mechanisms involved are beginning to be elucidated. However, SOCE is also involved is other aspects of cell migration with a less well-defined mechanistic understanding. Therefore, much remains to be learned regarding the role and regulation of SOCE in migrating cells.

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