scholarly journals Genetic defects in ion channels and neurological diseases in clinical, genetic and physiological aspects

2000 ◽  
Vol XXXII (1-2) ◽  
pp. 52-61
Author(s):  
A. L. Zefirov ◽  
E. I. Bogdanov ◽  
A. T. Zabbarova ◽  
M. A. Mukhamedyarov
Keyword(s):  
Ion Channels ◽  
Neurological Diseases ◽  
Genetic Defects ◽  
Clinical Genetic ◽  
Channel Proteins ◽  
Physiological Processes ◽  
Genes Encoding ◽  
Ion Channel Proteins ◽  
Angle Of View ◽  
Hereditary Neurological Diseases

Since the 90s, mutations in genes encoding ion channel proteins have been described. These mutations are responsible for the development of a number of neurological diseases called canalopathies (CP) [30, 36]. It is of interest to study the clinical features of hereditary neurological diseases, the pathogenesis of which are genetic defects in ion channels, from a single angle of view, as well as an attempt to analyze the probable physiological processes underlying these diseases. This approach may be important for a new systematization of these diseases, usually belonging to different groups, and for the development of a modern strategy for their therapy.

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?

Ion channels and disease

2020 ◽  
pp. 246-255
Author(s):  
Frances Ashcroft ◽  
Paolo Tammaro
Keyword(s):  
Ion Channels ◽  
Ion Channel ◽  
Single Channel ◽  
Cell Types ◽  
Channel Structure ◽  
Channel Proteins ◽  
Channel Function ◽  
Ion Channel Proteins ◽  
Single Channel Currents ◽  
Channel Currents

Ion channels are membrane proteins that act as gated pathways for the movement of ions across cell membranes. They are found in both surface and intracellular membranes and play essential roles in the physiology of all cell types. An ever-increasing number of human diseases are now known to be caused by defects in ion channel function. To understand how ion channel defects give rise to disease, it is helpful to understand how the ion channel proteins work. This chapter therefore considers what is known of ion channel structure, explains the properties of the single ion channel, and shows how single-channel currents give rise to action potentials and synaptic potentials.

scholarly journals Precise control of ion channel and gap junction expression is required for patterning of the regenerating axolotl limb

2020 ◽  
Vol 64 (10-11-12) ◽  
pp. 485-494
Author(s):  
Konstantinos Sousounis ◽  
Burcu Erdogan ◽  
Michael Levin ◽  
Jessica L. Whited
Keyword(s):  
Ion Channels ◽  
Gap Junctions ◽  
Ion Channel ◽  
Gap Junction ◽  
Regulation Of Gene Expression ◽  
Transcriptional Networks ◽  
Channel Proteins ◽  
Junction Protein ◽  
Ion Channel Proteins ◽  
Voltage Gradients

Axolotls and other salamanders have the capacity to regenerate lost tissue after an amputation or injury. Growth and morphogenesis are coordinated within cell groups in many contexts by the interplay of transcriptional networks and biophysical properties such as ion flows and voltage gradients. It is not, however, known whether regulators of a cell’s ionic state are involved in limb patterning at later stages of regeneration. Here we manipulated expression and activities of ion channels and gap junctions in vivo, in axolotl limb blastema cells. Limb amputations followed by retroviral infections were performed to drive expression of a human gap junction protein Connexin 26 (Cx26), potassium (Kir2.1-Y242F and Kv1.5) and sodium (NeoNav1.5) ion channel proteins along with EGFP control. Skeletal preparation revealed that overexpressing Cx26 caused syndactyly, while overexpression of ion channel proteins resulted in digit loss and structural abnormalities compared to EGFP expressing control limbs. Additionally, we showed that exposing limbs to the gap junction inhibitor lindane during the regeneration process caused digit loss. Our data reveal that manipulating native ion channel and gap junction function in blastema cells results in patterning defects involving the number and structure of the regenerated digits. Gap junctions and ion channels have been shown to mediate ion flows that control the endogenous voltage gradients which are tightly associated with the regulation of gene expression, cell cycle progression, migration, and other cellular behaviors. Therefore, we postulate that mis-expression of these channels may have disturbed this regulation causing uncoordinated cell behavior which results in morphological defects.

Ion channel proteins in mouse and human vestibular tissue

2005 ◽  
Vol 132 (6) ◽  
pp. 916-923 ◽  
Author(s):  
Karin Hotchkiss ◽  
Margaret Harvey ◽  
Mary Pacheco ◽  
Bernd Sokolowski
Keyword(s):  
Ion Channels ◽  
Ion Channel ◽  
Inner Ear ◽  
Potassium Ion ◽  
Β Subunit ◽  
Potassium Ion Channel ◽  
Channel Proteins ◽  
Ion Channel Proteins ◽  
Vestibular Endorgans ◽  
Α Subunits

BACKGROUND AND OBJECTIVE: Electrical activity in hair cells and neurons of the inner ear is necessary for the transduction and modulation of stimuli that impinge on the cochlea and vestibular endorgans of the inner ear. The underlying basis of this activity is pore-forming proteins in the membrane of excitable cells that allow the influx and efflux of various ions, including Na+, Ca2+, and K+, among others. These channels are critical to both electrical activity as well as the development of excitable cells because they may initiate long-term signals that are important in the maintenance and survival of these cells. We investigated the expression of several Shaker potassium ion channel proteins and an accessory β subunit in the vestibular endorgans of mouse and human. METHODS: Vestibular tissue consisting of cristae ampullares was harvested from adult and neonatal mice as well as from human subjects undergoing vestibular surgery. Western blot analysis and immunoprecipitation were used to identify the presence or absence, in mouse, of α subunits Kv1.2, Kv1.4, and Kv1.5 and of β subunit Kvβ1.1 in mouse. Coimmunoprecipitation was used to identify interactions between α and β subunits. Immunohistochemistry was used to localize Kv1.2 in mouse and human tissues. RESULTS: The presence of Kvα1.2 and Kvβ1.1 was confirmed in adult mouse crista ampullaris by Western blotting. Coimmunoprecipitation experiments showed that Kv1.2 and Kvβ1.1 interact in these tissues. Immunostaining localized Kv1.2 to regions within and extraneous to the sensory epithelium of mouse and human cristae ampullares. In comparison, Kv1.4 and Kv1.5 were not found in the crista ampullaris. CONCLUSIONS: We describe the presence, location, and interaction of various potassium ion channel α subunits and a β subunit. These data are initial descriptions of potassium ion channels in the mammalian vestibular system and begin to provide an understanding of the protein subunits that form ion channels of the mammalian inner ear. In addition, our data show that there are interactions that occur that may regulate the biophysical properties of these channels, thereby contributing to the diversity of channel function. This knowledge is critical to understanding the genes that encode these channels and finding cures for pathologies of hearing and balance. SIGNIFICANCE: We detail initial characteristics of potassium ion channel proteins including α subunits Kv1.2, Kv1.4, and Kv1.5 and β subunit Kvβ1.1 in mammalian vestibular tissue. This knowledge is critical to understanding the processing of vestibular stimuli and the regulation of endolymphatic function. Mutations of ion channels can cause neurological pathologies including auditory and vestibular disorders in humans.

Extraction of Auditory Information by Modulation of Neuronal Ion Channels

2018 ◽  
pp. 272-300
Author(s):  
Leonard K. Kaczmarek
Keyword(s):  
Ion Channels ◽  
Neuronal Firing ◽  
Auditory Information ◽  
Auditory Neurons ◽  
Complex Sound ◽  
Medial Nucleus ◽  
Rapid Changes ◽  
Genes Encoding ◽  
Kinetics Of ◽  
Trapezoid Body

All neurons express a subset of over seventy genes encoding potassium channel subunits. These channels have been studied in auditory neurons, particularly in the medial nucleus of the trapezoid body. The amplitude and kinetics of various channels in these neurons can be modified by the auditory environment. It has been suggested that such modulation is an adaptation of neuronal firing patterns to specific patterns of auditory inputs. Alternatively, such modulation may allow a group of neurons, all expressing the same set of channels, to represent a variety of responses to the same pattern of incoming stimuli. Such diversity would ensure that a small number of genetically identical neurons could capture and encode many aspects of complex sound, including rapid changes in timing and amplitude. This review covers the modulation of ion channels in the medial nucleus of the trapezoid body and how it may maximize the extraction of auditory information.All neurons express a subset of over seventy genes encoding potassium channel subunits. These channels have been studied in auditory neurons, particularly in the medial nucleus of the trapezoid body. The amplitude and kinetics of various channels in these neurons can be modified by the auditory environment. It has been suggested that such modulation is an adaptation of neuronal firing patterns to specific patterns of auditory inputs. Alternatively, such modulation may allow a group of neurons, all expressing the same set of channels, to represent a variety of responses to the same pattern of incoming stimuli. Such diversity would ensure that a small number of genetically identical neurons could capture and encode many aspects of complex sound, including rapid changes in timing and amplitude. This review covers the modulation of ion channels in the medial nucleus of the trapezoid body and how it may maximize the extraction of auditory information.

Acute O2 sensing through HIF2α-dependent expression of atypical cytochrome oxidase subunits in arterial chemoreceptors

2019 ◽  
Vol 13 (615) ◽  
pp. eaay9452 ◽  
Author(s):  
Alejandro Moreno-Domínguez ◽  
Patricia Ortega-Sáenz ◽  
Lin Gao ◽  
Olalla Colinas ◽  
Paula García-Flores ◽  
...  
Keyword(s):  
Ion Channels ◽  
Carotid Body ◽  
Acute Hypoxia ◽  
Mechanistic Explanation ◽  
Nerve Fibers ◽  
Adaptive Responses ◽  
Glomus Cells ◽  
Adult Mice ◽  
Genes Encoding ◽  
Regulation Of Breathing

Acute cardiorespiratory responses to O2 deficiency are essential for physiological homeostasis. The prototypical acute O2-sensing organ is the carotid body, which contains glomus cells expressing K+ channels whose inhibition by hypoxia leads to transmitter release and activation of nerve fibers terminating in the brainstem respiratory center. The mechanism by which changes in O2 tension modulate ion channels has remained elusive. Glomus cells express genes encoding HIF2α (Epas1) and atypical mitochondrial subunits at high levels, and mitochondrial NADH and reactive oxygen species (ROS) accumulation during hypoxia provides the signal that regulates ion channels. We report that inactivation of Epas1 in adult mice resulted in selective abolition of glomus cell responsiveness to acute hypoxia and the hypoxic ventilatory response. Epas1 deficiency led to the decreased expression of atypical mitochondrial subunits in the carotid body, and genetic deletion of Cox4i2 mimicked the defective hypoxic responses of Epas1-null mice. These findings provide a mechanistic explanation for the acute O2 regulation of breathing, reveal an unanticipated role of HIF2α, and link acute and chronic adaptive responses to hypoxia.

ChemInform Abstract: Synthetic Peptides as Models for Ion Channel Proteins

ChemInform ◽  
2010 ◽  
Vol 24 (32) ◽  
pp. no-no
Author(s):  
K. S. AKERFELDT ◽  
J. D. LEAR ◽  
Z. R. WASSERMAN ◽  
L. A. CHUNG ◽  
W. F. DEGRADO
Keyword(s):  
Ion Channel ◽  
Synthetic Peptides ◽  
Channel Proteins ◽  
Ion Channel Proteins

Activity of single ion channel proteins detected with a planar microstructure

2002 ◽  
Vol 81 (25) ◽  
pp. 4865-4867 ◽  
Author(s):  
Niels Fertig ◽  
Michèle Klau ◽  
Michael George ◽  
Robert H. Blick ◽  
Jan C. Behrends
Keyword(s):  
Ion Channel ◽  
Channel Proteins ◽  
Ion Channel Proteins

Congenital neutropenia

Hematology ◽  
2009 ◽  
Vol 2009 (1) ◽  
pp. 344-350 ◽  
Author(s):  
Christoph Klein
Keyword(s):  
Ribosomal Proteins ◽  
Mitochondrial Proteins ◽  
Phenotypic Traits ◽  
Genetic Defects ◽  
Congenital Neutropenia ◽  
Lysosomal Function ◽  
Genes Encoding ◽  
And Function ◽  
Neutrophil Differentiation ◽  
Remarkable Progress

Abstract Congenital neutropenia comprises a variety of genetically heterogeneous phenotypic traits. Molecular elucidation of the underlying genetic defects has yielded important insights into the physiology of neutrophil differentiation and function. Non-syndromic variants of congenital neutropenia are caused by mutations in ELA2, HAX1, GFI1, or WAS. Syndromic variants of congenital neutropenia may be due to mutations in genes controlling glucose metabolism (SLC37A4, G6PC3) or lysosomal function (LYST, RAB27A, ROBLD3/p14, AP3B1, VPS13B). Furthermore, defects in genes encoding ribosomal proteins (SBDS, RMRP) and mitochondrial proteins (AK2, TAZ) are associated with congenital neutropenia syndromes. Despite remarkable progress in the field, many patients with congenital neutropenia cannot yet definitively be classified by genetic terms. This review addresses diagnostic and therapeutic aspects of congenital neutropenia and covers recent molecular and pathophysiological insights of selected congenital neutropenia syndromes.

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