Ion Channel Degeneracy, Variability, and Covariation in Neuron and Circuit Resilience

2021 ◽  
Vol 44 (1) ◽  
Author(s):  
Jean-Marc Goaillard ◽  
Eve Marder
Keyword(s):  
Ion Channels ◽  
Ion Channel ◽  
Time Dependent ◽  
Annual Review ◽  
Publication Date ◽  
Cell Type ◽  
Intrinsic Properties ◽  
Neuronal Function ◽  
Channel Conductance ◽  
Pharmacological Manipulation

The large number of ion channels found in all nervous systems poses fundamental questions concerning how the characteristic intrinsic properties of single neurons are determined by the specific subsets of channels they express. All neurons display many different ion channels with overlapping voltage- and time-dependent properties. We speculate that these overlapping properties promote resilience in neuronal function. Individual neurons of the same cell type show variability in ion channel conductance densities even though they can generate reliable and similar behavior. This complicates a simple assignment of function to any conductance and is associated with variable responses of neurons of the same cell type to perturbations, deletions, and pharmacological manipulation. Ion channel genes often show strong positively correlated expression, which may result from the molecular and developmental rules that determine which ion channels are expressed in a given cell type. Expected final online publication date for the Annual Review of Neuroscience, Volume 44 is July 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Uterine Excitability and Ion Channels and Their Changes with Gestation and Hormonal Environment

2020 ◽  
Vol 83 (1) ◽  
Author(s):  
Susan Wray ◽  
Sarah Arrowsmith
Keyword(s):  
Ion Channels ◽  
Inward Rectifier ◽  
Cation Channels ◽  
Annual Review ◽  
Publication Date ◽  
K Channels ◽  
Voltage Gated ◽  
New Findings ◽  
Voltage Dependent ◽  
Pore Domain

We address advances in the understanding of myometrial physiology, focusing on excitation and the effects of gestation on ion channels and their relevance to labor. This review moves through pioneering studies to exciting new findings. We begin with the myometrium and its myocytes and describe how excitation might initiate and spread in this myogenic smooth muscle. We then review each of the ion channels in the myometrium: L- and T-type Ca2+ channels, KATP (Kir6) channels, voltage-dependent K channels (Kv4, Kv7, and Kv11), twin-pore domain K channels (TASK, TREK), inward rectifier Kir7.1, Ca2+-activated K+ channels with large (KCNMA1, Slo1), small (KCNN1–3), and intermediate (KCNN4) conductance, Na-activated K channels (Slo2), voltage-gated (SCN) Na+ and Na+ leak channels, nonselective (NALCN) channels, the Na K-ATPase, and hyperpolarization-activated cation channels. We finish by assessing how three key hormones— oxytocin, estrogen, and progesterone—modulate and integrate excitability throughout gestation. Expected final online publication date for the Annual Review of Physiology, Volume 83 is February 10, 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

scholarly journals Double and Charge-Transfer Excitations in Time-Dependent Density Functional Theory

2021 ◽  
Vol 73 (1) ◽  
Author(s):  
Neepa T. Maitra
Keyword(s):  
Density Functional Theory ◽  
Charge Transfer ◽  
Density Functional ◽  
System Size ◽  
Time Dependent ◽  
Annual Review ◽  
Publication Date ◽  
Functional Theory ◽  
Dependent Density ◽  
Made In

Time-dependent density functional theory has emerged as a method of choice for calculations of spectra and response properties in physics, chemistry, and biology, with its system-size scaling enabling computations on systems much larger than otherwise possible. While increasingly complex and interesting systems have been successfully tackled with relatively simple functional approximations, there has also been increasing awareness that these functionals tend to fail for certain classes of approximations. Here I review the fundamental challenges the approximate functionals have in describing double excitations and charge-transfer excitations, which are two of the most common impediments for the theory to be applied in a black-box way. At the same time, I describe the progress made in recent decades in developing functional approximations that give useful predictions for these excitations. Expected final online publication date for the Annual Review of Physical Chemistry, Volume 73 is April 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

The Diverse Physiological Functions of Mechanically Activated Ion Channels in Mammals

2021 ◽  
Vol 84 (1) ◽  
Author(s):  
Kate Poole
Keyword(s):  
Plasma Membrane ◽  
Ion Channels ◽  
Mammalian Cells ◽  
Annual Review ◽  
Publication Date ◽  
Research Focus ◽  
Ionic Flux ◽  
Touch Sensation ◽  
Mechanical Sensing

Many aspects of mammalian physiology are mechanically regulated. One set of molecules that can mediate mechanotransduction are the mechanically activated ion channels. These ionotropic force sensors are directly activated by mechanical inputs, resulting in ionic flux across the plasma membrane. While there has been much research focus on the role of mechanically activated ion channels in touch sensation and hearing, recent data have highlighted the broad expression pattern of these molecules in mammalian cells. Disruption of mechanically activated channels has been shown to impact ( a) the development of mechanoresponsive structures, ( b) acute mechanical sensing, and ( c) mechanically driven homeostatic maintenance in multiple tissue types. The diversity of processes impacted by these molecules highlights the importance of mechanically activated ion channels in mammalian physiology. Expected final online publication date for the Annual Review of Physiology, Volume 84 is February 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Cystic Fibrosis and the Cells of the Airway Epithelium: What Are Ionocytes and What Do They Do?

2021 ◽  
Vol 17 (1) ◽  
Author(s):  
Viral S. Shah ◽  
Raghu R. Chivukula ◽  
Brian Lin ◽  
Avinash Waghray ◽  
Jayaraj Rajagopal
Keyword(s):  
Cystic Fibrosis ◽  
Epithelial Cell ◽  
Airway Epithelial Cell ◽  
Genetic Manipulation ◽  
Airway Epithelial Cells ◽  
Annual Review ◽  
Publication Date ◽  
Airway Epithelial ◽  
Cell Type ◽  
Epithelial Cell Type

Cystic fibrosis (CF) is caused by defects in an anion channel, the cystic fibrosis transmembrane conductance regulator (CFTR). Recently, a new airway epithelial cell type has been discovered and dubbed the pulmonary ionocyte. Unexpectedly, these ionocytes express higher levels of CFTR than any other airway epithelial cell type. However, ionocytes are not the sole CFTR-expressing airway epithelial cells, and CF-associated disease genes are in fact expressed in multiple airway epithelial cell types. The experimental depletion of ionocytes perturbs epithelial physiology in the mouse trachea, but the role of these rare cells in the pathogenesis of human CF remains mysterious. Ionocytes have been described in diverse tissues (kidney and inner ear) and species (frog and fish). We draw on these prior studies to suggest potential roles of airway ionocytes in health and disease. A complete understanding of ionocytes in the mammalian airway will ultimately depend on cell type–specific genetic manipulation Expected final online publication date for the Annual Review of Pathology: Mechanisms of Disease, Volume 17 is January 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

How Many Cell Types Are in the Kidney and What Do They Do?

2021 ◽  
Vol 84 (1) ◽  
Author(s):  
Michael S. Balzer ◽  
Tibor Rohacs ◽  
Katalin Susztak
Keyword(s):  
Interstitial Cell ◽  
Cell Types ◽  
Annual Review ◽  
Publication Date ◽  
Cell Type ◽  
Acid Base Balance ◽  
New Era ◽  
Type Definition ◽  
Base Balance ◽  
Different Cell Types

The kidney maintains electrolyte, water, and acid-base balance, eliminates foreign and waste compounds, regulates blood pressure, and secretes hormones. There are at least 16 different highly specialized epithelial cell types in the mammalian kidney. The number of specialized endothelial cells, immune cells, and interstitial cell types might even be larger. The concerted interplay between different cell types is critical for kidney function. Traditionally, cells were defined by their function or microscopical morphological appearance. With the advent of new single-cell modalities such as transcriptomics, epigenetics, metabolomics, and proteomics we are entering into a new era of cell type definition. This new technological revolution provides new opportunities to classify cells in the kidney and understand their functions. Expected final online publication date for the Annual Review of Physiology, Volume 84 is February 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

scholarly journals Single-neuron models linking electrophysiology, morphology and transcriptomics across cortical cell types

2020 ◽  
Author(s):  
Anirban Nandi ◽  
Tom Chartrand ◽  
Werner Van Geit ◽  
Anatoly Buchin ◽  
Zizhen Yao ◽  
...  
Keyword(s):  
Ion Channel ◽  
Single Cell ◽  
Single Neuron ◽  
Cell Types ◽  
Cell Models ◽  
Cell Type ◽  
Channel Conductance ◽  
Neuron Models ◽  
Inhibitory Cell

AbstractIdentifying the cell types constituting brain circuits is a fundamental question in neuroscience and motivates the generation of taxonomies based on electrophysiological, morphological and molecular single cell properties. Establishing the correspondence across data modalities and understanding the underlying principles has proven challenging. Bio-realistic computational models offer the ability to probe cause-and-effect and have historically been used to explore phenomena at the single-neuron level. Here we introduce a computational optimization workflow used for the generation and evaluation of more than 130 million single neuron models with active conductances. These models were based on 230 in vitro electrophysiological experiments followed by morphological reconstruction from the mouse visual cortex. We show that distinct ion channel conductance vectors exist that distinguish between major cortical classes with passive and h-channel conductances emerging as particularly important for classification. Next, using models of genetically defined classes, we show that differences in specific conductances predicted from the models reflect differences in gene expression in excitatory and inhibitory cell types as experimentally validated by single-cell RNA-sequencing. The differences in these conductances, in turn, explain many of the electrophysiological differences observed between cell types. Finally, we show the robustness of the herein generated single-cell models as representations and realizations of specific cell types in face of biological variability and optimization complexity. Our computational effort generated models that reconcile major single-cell data modalities that define cell types allowing for causal relationships to be examined.HighlightsGeneration and evaluation of more than 130 million single-cell models with active conductances along the reconstructed morphology faithfully recapitulate the electrophysiology of 230 in vitro experiments.Optimized ion channel conductances along the cellular morphology (‘all-active’) are characteristic of model complexity and offer enhanced biophysical realism.Ion channel conductance vectors of all-active models classify transcriptomically defined cell-types.Cell type differences in ion channel conductances predicted by the models correlate with experimentally measured single-cell gene expression differences in inhibitory (Pvalb, Sst, Htr3a) and excitatory (Nr5a1, Rbp4) classes.A set of ion channel conductances identified by comparing between cell type model populations explain electrophysiology differences between these types in simulations and brain slice experiments.All-active models recapitulate multimodal properties of excitatory and inhibitory cell types offering a systematic and causal way of linking differences between them.

scholarly journals Sensitivity Analysis of Ion Channel Conductance on Myocardial Electromechanical Delay: Computational Study

2021 ◽  
Vol 12 ◽  
Author(s):  
Ali Ikhsanul Qauli ◽  
Aroli Marcellinus ◽  
Ki Moo Lim
Keyword(s):  
Ion Channels ◽  
Action Potential ◽  
Ion Channel ◽  
Computational Study ◽  
Cardiac Cells ◽  
Delayed Rectifier ◽  
Channel Conductance ◽  
Electromechanical Delay ◽  
Major Ion ◽  
Ventricular Cells

It is well known that cardiac electromechanical delay (EMD) can cause dyssynchronous heart failure (DHF), a prominent cardiovascular disease (CVD). This work computationally assesses the conductance variation of every ion channel on the cardiac cell to give rise to EMD prolongation. The electrical and mechanical models of human ventricular tissue were simulated, using a population approach with four conductance reductions for each ion channel. Then, EMD was calculated by determining the difference between the onset of action potential and the start of cell shortening. Finally, EMD data were put into the optimized conductance dimensional stacking to show which ion channel has the most influence in elongating the EMD. We found that major ion channels, such as L-type calcium (CaL), slow-delayed rectifier potassium (Ks), rapid-delayed rectifier potassium (Kr), and inward rectifier potassium (K1), can significantly extend the action potential duration (APD) up to 580 ms. Additionally, the maximum intracellular calcium (Cai) concentration is greatly affected by the reduction in channel CaL, Ks, background calcium, and Kr. However, among the aforementioned major ion channels, only the CaL channel can play a superior role in prolonging the EMD up to 83 ms. Furthermore, ventricular cells with long EMD have been shown to inherit insignificant mechanical response (in terms of how strong the tension can grow and how far length shortening can go) compared with that in normal cells. In conclusion, despite all variations in every ion channel conductance, only the CaL channel can play a significant role in extending EMD. In addition, cardiac cells with long EMD tend to have inferior mechanical responses due to a lack of Cai compared with normal conditions, which are highly likely to result in a compromised pump function of the heart.

Endogenous Retroviruses Drive Resistance and Promotion of Exogenous Retroviral Homologs

2020 ◽  
Vol 9 (1) ◽  
Author(s):  
Elliott S. Chiu ◽  
Sue VandeWoude
Keyword(s):  
Immune Modulation ◽  
Viral Infections ◽  
Viral Evolution ◽  
Endogenous Retroviruses ◽  
Annual Review ◽  
Publication Date ◽  
Biological Functions ◽  
Self Tolerance ◽  
Vertebrate Hosts ◽  
Insight Into

Endogenous retroviruses (ERVs) serve as markers of ancient viral infections and provide invaluable insight into host and viral evolution. ERVs have been exapted to assist in performing basic biological functions, including placentation, immune modulation, and oncogenesis. A subset of ERVs share high nucleotide similarity to circulating horizontally transmitted exogenous retrovirus (XRV) progenitors. In these cases, ERV–XRV interactions have been documented and include ( a) recombination to result in ERV–XRV chimeras, ( b) ERV induction of immune self-tolerance to XRV antigens, ( c) ERV antigen interference with XRV receptor binding, and ( d) interactions resulting in both enhancement and restriction of XRV infections. Whereas the mechanisms governing recombination and immune self-tolerance have been partially determined, enhancement and restriction of XRV infection are virus specific and only partially understood. This review summarizes interactions between six unique ERV–XRV pairs, highlighting important ERV biological functions and potential evolutionary histories in vertebrate hosts. Expected final online publication date for the Annual Review of Animal Biosciences, Volume 9 is February 16, 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Perturbation of Ion Channel Conductance Alters the Hypnotic Response to the α2-Adrenergic Agonist Dexmedetomidine in the Locus Coeruleus of the Rat

1994 ◽  
Vol 81 (6) ◽  
pp. 1527-1534 ◽  
Author(s):  
Carla Nacif-Coelho ◽  
Christiane Correa-Sales ◽  
Louise Lenoir Chang ◽  
Mervyn Maze
Keyword(s):  
Ion Channel ◽  
Locus Coeruleus ◽  
Channel Conductance ◽  
Adrenergic Agonist

Advancing Socioeconomic Rights Through Interdisciplinary Factfinding: Opportunities and Challenges

2021 ◽  
Vol 17 (1) ◽  
Author(s):  
Sarah Knuckey ◽  
Joshua D. Fisher ◽  
Amanda M. Klasing ◽  
Tess Russo ◽  
Margaret L. Satterthwaite
Keyword(s):  
Human Rights ◽  
Mixed Methods ◽  
Social Science ◽  
Science Volume ◽  
Lessons Learned ◽  
Limited Resources ◽  
Annual Review ◽  
Publication Date ◽  
Socioeconomic Rights ◽  
Human Rights Movement

The human rights movement is increasingly using interdisciplinary, multidisciplinary, mixed-methods, and quantitative factfinding. There has been too little analysis of these shifts. This article examines some of the opportunities and challenges of these methods, focusing on the investigation of socioeconomic human rights. By potentially expanding the amount and types of evidence available, factfinding's accuracy and persuasiveness can be strengthened, bolstering rights claims. However, such methods can also present significant challenges and may pose risks in individual cases and to the human rights movement generally. Interdisciplinary methods can be costly in human, financial, and technical resources; are sometimes challenging to implement; may divert limited resources from other work; can reify inequalities; may produce “expertise” that disempowers rightsholders; and could raise investigation standards to an infeasible or counterproductive level. This article includes lessons learned and questions to guide researchers and human rights advocates considering mixed-methods human rights factfinding. Expected final online publication date for the Annual Review of Law and Social Science, Volume 17 is October 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

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