Gating of Ion Channels

Author(s):  
Rene Barro-Soria

Excitable cells, such as neurons and muscles, use ion channels to generate electrical and chemical signals that underlie their functions. Examples include the electrical signals underlying the complex neuronal circuitry in the brain, the secretion of hormones and neurotransmitters, skeletal and cardiac muscle contraction, and the signaling events that lead to fertility. Because of their pivotal role in cellular signaling and electrical excitability, a major goal in modern biology has been to determine the physical properties that control and modulate ion channel function. This chapter briefly reviews classical works about the gating of ion channels. Furthermore, it discusses some innovative approaches that when combined with biophysical and mathematical simulations have contributed to the current understanding of channel gating.

Author(s):  
Elena A. Morachevskaya ◽  
Anastasia V. Sudarikova

Ion channels in plasma membrane play a principal role in different physiological processes, including cell volume regulation, signal transduction and modulation of membrane potential in living cells. Actin-based cytoskeleton, which exists in a dynamic balance between monomeric and polymeric forms (globular and fibrillar actin), can be directly or indirectly involved in various cellular responses including modulation of ion channel activity. In this mini-review, we present an overview of the role of submembranous actin dynamics in the regulation of ion channels in excitable and non-excitable cells. Special attention is focused on the important data about the involvement of actin assembly/disassembly and some actin-binding proteins in the control of the Epithelial Na+ Channel (ENaC) and mechanosensitive Piezo channels whose integral activity has potential impact on membrane transport and multiple coupled cellular reactions. Growing evidence suggests that actin elements of the cytoskeleton can represent a "converging point" of various signaling pathways modulating the activity of ion transport proteins in cell membranes.


2005 ◽  
Vol 8 (6) ◽  
pp. 607-614 ◽  
Author(s):  
Dawna Duncan Armstrong

Our understanding of the pathogenesis of the neuropathology of epilepsy has been challenged by a need to separate the “lesions” that cause epilepsy from the “lesions” that are produced by the epilepsy. Significant clinical, genetic, pathologic, and experimental studies of Ammon horn sclerosis (AHS) suggest that AHS is the result and cause of seizures. The data support the idea that seizures cause alterations in cell numbers, cell shape, and organization of neuronal circuitry, thus setting up an identifiable seizure-genic focus. As such, AHS represents a slowly progressive lesion and a search for the cause of the initiating seizure has led to the identification of ion channel mutations. In this report, the neuropathology of other conditions associated with intractable epilepsy is considered, suggesting that in them similar epilepsy-produced alterations in microarchitecture can be observed. The idea is important to define the optimum time for epilepsy surgery and the underlying etiology of these seizure-genic lesions.


2020 ◽  
Vol 37 (5) ◽  
pp. 703-716
Author(s):  
Saumya Bajaj ◽  
Seow Theng Ong ◽  
K. George Chandy

Natural products harnessed from the diverse universe of compounds within the bioenvironment are being used to modulate ion channels, a vast super-family of membrane proteins that play critical physiological roles in excitable and non-excitable cells.


Author(s):  
Jim R. Wilson ◽  
Neil A. Duncan

All cells have a membrane potential; this voltage difference arises from the different intracellular and extracellular ion concentrations. In excitable tissue the cell membranes contain ion channels which control the movement of ions and hence control the cell’s membrane potential. Extensive measurements of the electrophysiology of excitable cells has allowed considerable understanding of the ion channels. The Hodgkin-Huxley model [1] was developed from measurements on a squid nerve axon, and it quantifies the changes in membrane conductance due to the opening and closing of specific ion channels. This model has been very successful in describing the electrical behaviour of neurons. Ion channels also exist in non-excitable tissue cells. Patch clamp experiments have demonstrated that ion channels in chondrocytes influence cell’s membrane potential [2]; controls the influx of Ca2+ [3] and may regulate cell proliferation [2]. The objective of this research was to develop a model of ion channel behaviour for connective tissue cells based on the Hodgkin-Huxley model, and to apply this model to reported patch clamp measurements of articular chondrocytes.


2004 ◽  
Vol 378 (3) ◽  
pp. 717-726 ◽  
Author(s):  
Stéphanie MOUHAT ◽  
Besma JOUIROU ◽  
Amor MOSBAH ◽  
Michel DE WAARD ◽  
Jean-Marc SABATIER

Animal toxins acting on ion channels of excitable cells are principally highly potent short peptides that are present in limited amounts in the venoms of various unrelated species, such as scorpions, snakes, sea anemones, spiders, insects, marine cone snails and worms. These toxins have been used extensively as invaluable biochemical and pharmacological tools to characterize and discriminate between the various ion channel types that differ in ionic selectivity, structure and/or cell function. Alongside the huge molecular and functional diversity of ion channels, a no less impressive structural diversity of animal toxins has been indicated by the discovery of an increasing number of polypeptide folds that are able to target these ion channels. Indeed, it appears that these peptide toxins have evolved over time on the basis of clearly distinct architectural motifs, in order to adapt to different ion channel modulating strategies (pore blockers compared with gating modifiers). Herein, we provide an up-to-date overview of the various types of fold from animal toxins that act on ion channels selective for K+, Na+, Ca2+ or Cl− ions, with special emphasis on disulphide bridge frameworks and structural motifs associated with these peptide folds.


Author(s):  
Katharina Held ◽  
Balázs István Tóth

Already for centuries, humankind is driven to understand the physiological and pathological mechanisms that occur in our brains. Today, we know that ion channels play an essential role in the regulation of neural processes and control many functions of the central nervous system. Ion channels present a diverse group of membrane-spanning proteins that allow ions to penetrate the insulating cell membrane upon opening of their channel pores. This regulated ion permeation results in different electrical and chemical signals that are necessary to maintain physiological excitatory and inhibitory processes in the brain. Therefore, it is no surprise that disturbances in the functions of cerebral ion channels can result in a plethora of neurological disorders, which present a tremendous health care burden for our current society. The identification of ion channel-related brain disorders also fuel the research into the roles of ion channel proteins in various brain states. In the last decade, mounting evidence has been collected that indicates a pivotal role for transient receptor potential (TRP) ion channels in the development and various physiological functions of the central nervous system. For instance, TRP channels modulate neurite growth, synaptic plasticity and integration, and are required for neuronal survival. Moreover, TRP channels are involved in numerous neurological disorders. TRPM3 belongs to the melastatin subfamily of TRP channels and represents a non-selective cation channel that can be activated by several different stimuli, including the neurosteroid pregnenolone sulfate, osmotic pressures and heat. The channel is best known as a peripheral nociceptive ion channel that participates in heat sensation. However, recent research identifies TRPM3 as an emerging new player in the brain. In this review, we summarize the available data regarding the roles of TRPM3 in the brain, and correlate these data with the neuropathological processes in which this ion channel may be involved.


1992 ◽  
Vol 70 (S1) ◽  
pp. S223-S238 ◽  
Author(s):  
H. Sontheimer

The electrophysiologist's view of brain astrocytes has changed markedly in recent years. In the past astrocytes were viewed as passive, K+ selective cells, but it is now evident that they are capable of expressing voltage- and ligand-activated channels previously thought to be restricted to neurons. The functional importance of most of these ion channels is not understood at present. However, from studies of astrocytes cultured from different species and brain regions, we learned that like their neuronal counterparts astrocytes are a heterogeneous group of brain cells showing similar heterogeneity in their ion-channel expression. Not only are subpopulations of astrocytes within areas of the brain equipped with specific sets of ion channels but, furthermore, regional heterogeneity is apparent. In addition, astrocyte ion channel expression is dynamic and changes during development. Some ion channels are only expressed postnatally, yet others appear to be expressed only during certain stages of development. Interestingly, the expression of some astrocyte channels, including Na+, Ca2+, and some K+ channels, appears to be controlled by neurons via mechanisms that are presently unknown. Some studies suggest roles for astrocyte channels in basic cell processes such as cell proliferation. Thus, although the role of some astrocyte channels remains unclear, our understanding of astrocyte physiology is starting to take shape and points towards roles of ion channels not involved in electrogenesis.Key words: astrocyte, ion channel, development, review, transmitter receptor.


2017 ◽  
Author(s):  
Jan Kubanek ◽  
Poojan Shukla ◽  
Alakananda Das ◽  
Stephen A. Baccus ◽  
Miriam B. Goodman

AbstractFocused ultrasound has been shown to stimulate excitable cells, but the biophysical mechanisms behind this phenomenon remain poorly understood. To provide additional insight, we devised a behavioral-genetic assay applied to the well-characterized nervous system of C. elegans nematodes. We found that pulsed ultrasound elicits robust reversal behavior in wild-type animals in a pressure-, duration-, and pulse protocol-dependent manner. Responses were preserved in mutants unable to sense thermal fluctuations and absent in mutants lacking neurons required for mechanosensation. Additionally, we found that the worm‘s response to ultrasound pulses rests on the expression of MEC-4, a DEG/ENaC/ASIC ion channel required for touch sensation. Consistent with prior studies of MEC-4-dependent currents in vivo, the worm’s response was optimal for pulses repeated 300 to 1000 times per second. Based on these findings, we conclude that mechanical, rather than thermal stimulation accounts for behavioral responses. Further, we propose that acoustic radiation force governs the response to ultrasound in a manner that depends on the touch receptor neurons and MEC-4-dependent ion channels. Our findings illuminate a complete pathway of ultrasound action, from the forces generated by propagating ultrasound to an activation of a specific ion channel. The findings further highlight the importance of optimizing ultrasound pulsing protocols when stimulating neurons via ion channels with mechanosensitive properties.Significance StatementHow ultrasound influences neurons and other excitable cells has remained a mystery for decades. Although it is widely understood that ultrasound can heat tissues and induce mechanical strain, whether or not neuronal activation depends on heat, mechanical force, or both physical factors is not known. We harnessed C. elegans nematodes and their extraordinary sensitivity to thermal and mechanical stimuli to address this question. Whereas thermosensory mutants respond to ultrasound similar to wild-type animals, mechanosensory mutants were insensitive to ultrasound stimulation. Additionally, stimulus parameters that accentuate mechanical effects were more effective than those producing more heat. These findings highlight a mechanical nature of the effect of ultrasound on neurons and suggest specific ways to optimize stimulation protocols in specific tissues.


2021 ◽  
Vol 10 (6) ◽  
pp. 1239
Author(s):  
Alexandru Cojocaru ◽  
Emilia Burada ◽  
Adrian-Tudor Bălșeanu ◽  
Alexandru-Florian Deftu ◽  
Bogdan Cătălin ◽  
...  

As the average age and life expectancy increases, the incidence of both acute and chronic central nervous system (CNS) pathologies will increase. Understanding mechanisms underlying neuroinflammation as the common feature of any neurodegenerative pathology, we can exploit the pharmacology of cell specific ion channels to improve the outcome of many CNS diseases. As the main cellular player of neuroinflammation, microglia play a central role in this process. Although microglia are considered non-excitable cells, they express a variety of ion channels under both physiological and pathological conditions that seem to be involved in a plethora of cellular processes. Here, we discuss the impact of modulating microglia voltage-gated, potential transient receptor, chloride and proton channels on microglial proliferation, migration, and phagocytosis in neurodegenerative diseases.


Author(s):  
Ali Momin ◽  
Shahrzad Bahrampour ◽  
Hyun-Kee Min ◽  
Xin Chen ◽  
Xian Wang ◽  
...  

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