Molecular Physiology of Low-Voltage-Activated T-type Calcium Channels

2003 ◽  
Vol 83 (1) ◽  
pp. 117-161 ◽  
Author(s):  
Edward Perez-Reyes
Keyword(s):  
Plasma Membrane ◽  
Action Potentials ◽  
Low Voltage ◽  
Absence Epilepsy ◽  
Molecular Physiology ◽  
Comprehensive Description ◽  
Cellular Processes ◽  
Repeat Structure ◽  
Intracellular Ca ◽  
Low Threshold

T-type Ca2+ channels were originally called low-voltage-activated (LVA) channels because they can be activated by small depolarizations of the plasma membrane. In many neurons Ca2+ influx through LVA channels triggers low-threshold spikes, which in turn triggers a burst of action potentials mediated by Na+ channels. Burst firing is thought to play an important role in the synchronized activity of the thalamus observed in absence epilepsy, but may also underlie a wider range of thalamocortical dysrhythmias. In addition to a pacemaker role, Ca2+ entry via T-type channels can directly regulate intracellular Ca2+ concentrations, which is an important second messenger for a variety of cellular processes. Molecular cloning revealed the existence of three T-type channel genes. The deduced amino acid sequence shows a similar four-repeat structure to that found in high-voltage-activated (HVA) Ca2+ channels, and Na+ channels, indicating that they are evolutionarily related. Hence, the α1-subunits of T-type channels are now designated Cav3. Although mRNAs for all three Cav3 subtypes are expressed in brain, they vary in terms of their peripheral expression, with Cav3.2 showing the widest expression. The electrophysiological activities of recombinant Cav3 channels are very similar to native T-type currents and can be differentiated from HVA channels by their activation at lower voltages, faster inactivation, slower deactivation, and smaller conductance of Ba2+. The Cav3 subtypes can be differentiated by their kinetics and sensitivity to block by Ni2+. The goal of this review is to provide a comprehensive description of T-type currents, their distribution, regulation, pharmacology, and cloning.

T-Type Ca2+ Channels in Normal and Abnormal Brain Functions

2013 ◽  
Vol 93 (3) ◽  
pp. 961-992 ◽  
Author(s):  
Eunji Cheong ◽  
Hee-Sup Shin
Keyword(s):  
Low Voltage ◽  
Signal Transmission ◽  
Absence Epilepsy ◽  
Resting Membrane Potential ◽  
Brain Functions ◽  
Central Neurons ◽  
Processing Pathways ◽  
Low Threshold ◽  
Pain Signal

Low-voltage-activated T-type Ca2+ channels are widely expressed in various types of neurons. Once deinactivated by hyperpolarization, T-type channels are ready to be activated by a small depolarization near the resting membrane potential and, therefore, are optimal for regulating the excitability and electroresponsiveness of neurons under physiological conditions near resting states. Ca2+ influx through T-type channels engenders low-threshold Ca2+ spikes, which in turn trigger a burst of action potentials. Low-threshold burst firing has been implicated in the synchronization of the thalamocortical circuit during sleep and in absence seizures. It also has been suggested that T-type channels play an important role in pain signal transmission, based on their abundant expression in pain-processing pathways in peripheral and central neurons. In this review, we will describe studies on the role of T-type Ca2+ channels in the physiological as well as pathological generation of brain rhythms in sleep, absence epilepsy, and pain signal transmission. Recent advances in studies of T-type channels in the control of cognition will also be briefly discussed.

Low-Voltage-Activated Calcium Current Does Not Regulate the Firing Behavior in Paired Mechanosensory Neurons With Different Adaptation Properties

2000 ◽  
Vol 83 (2) ◽  
pp. 746-753 ◽  
Author(s):  
Shin-Ichi Sekizawa ◽  
Andrew S. French ◽  
Päivi H. Torkkeli
Keyword(s):  
Action Potential ◽  
Action Potentials ◽  
Low Voltage ◽  
Firing Frequency ◽  
Oscillatory Behavior ◽  
Firing Behavior ◽  
Single Action ◽  
Synaptic Excitation ◽  
Intracellular Ca ◽  
The Difference

Low-voltage-activated Ca2+ currents (LVA- I Ca) are believed to perform several roles in neurons such as lowering the threshold for action potentials, promoting burst firing and oscillatory behavior, and enhancing synaptic excitation. They also may allow rapid increases in intracellular Ca2+ concentration. We discovered LVA- I Ca in both members of paired mechanoreceptor neurons in a spider, where one neuron adapts rapidly (Type A) and the other slowly (Type B) in response to a step stimulus. To learn if I Ca contributed to the difference in adaptation behavior, we studied the kinetics of I Ca from isolated somata under single-electrode voltage-clamp and tested its physiological function under current clamp. LVA- I Ca was large enough to fire single action potentials when all other voltage-activated currents were blocked, but we found no evidence that it regulated firing behavior. LVA- I Ca did not lower the action potential threshold or affect firing frequency. Previous experiments have failed to find Ca2+-activated K+ current ( I K(Ca)) in the somata of these neurons, so it is also unlikely that LVA- I Ca interacts with I K(Ca) to produce oscillatory behavior. We conclude that LVA-Ca2+ channels in the somata, and possible in the dendrites, of these neurons open in response to the depolarization caused by receptor current and by the voltage-activated Na+ current ( I Na) that produces action potential(s). However, the role of the increased intracellular Ca2+ concentration in neuronal function remains enigmatic.

scholarly journals Molecular physiology and pathology of Ca2+-conducting channels in the plasma membrane of mammalian sperm

Reproduction ◽  
2005 ◽  
Vol 129 (3) ◽  
pp. 251-262 ◽  
Author(s):  
Ricardo Felix
Keyword(s):  
Plasma Membrane ◽  
Acrosome Reaction ◽  
Current Evidence ◽  
Molecular Physiology ◽  
Mammalian Sperm ◽  
Fertilizing Ability ◽  
Intracellular Ca ◽  
Gene Defects ◽  
Sperm Fertilizing Ability ◽  
Sperm Functions

Current evidence indicates that mechanisms controlling the intracellular Ca2+concentration play pivotal roles in determining sperm fertilizing ability. Multiple Ca2+-permeable channels have been identified and characterized in the plasma membrane and in the acrosome membrane of mammalian sperm. This review summarizes the recent findings and assesses the evidence suggesting that these channels play roles in controlling a host of sperm functions ranging from motility to the acrosome reaction, and describes recent advances in the identification of the underlying gene defects of inherited sperm Ca2+channelopathies.

vitreal cells and specialized phagocytes in the chick embryo retina: A TEM and SEM study

1990 ◽  
Vol 48 (3) ◽  
pp. 330-331
Author(s):  
M.A. Cuadros ◽  
M.J. Martinez-Guerrero ◽  
A. Rios
Keyword(s):  
Cell Death ◽  
Plasma Membrane ◽  
Acid Phosphatase ◽  
Chick Embryo ◽  
Basement Membrane ◽  
Sem Images ◽  
Intimate Contact ◽  
Cellular Processes ◽  
Sem Study ◽  
Free Cells

In the chick embryo retina (days 3-4 of incubation), coinciding with an increase in cell death, specialized phagocytes characterized by intense acid phosphatase activity have been described. In these preparations, all free cells in the vitreal humor (vitreal cells) were strongly labeled. Conventional TEM and SEM techniques were used to characterize them and attempt to determine their relationship with retinal phagocytes.Two types of vitreal cells were distinguished. The first are located at some distance from the basement membrane of the neuroepithelium, and are rounded, with numerous vacuoles and thin cytoplasmic prolongations. Images of exo- and or endocytosis were frequent; the cells showed a well-developed Golgi apparatus (Fig. 1) In SEM images, the cells was covered with short cellular processes (Fig. 3). Cells lying parallel to or alongside the basement membrane are elongated. The plasma membrane is frequently in intimate contact with the basement membrane. These cells have generally a large cytoplasmic expansion (Fig. 5).

scholarly journals Putative PmrA and PmcA are important for normal growth, morphogenesis and cell wall integrity, but not for viability in Aspergillus nidulans

Microbiology ◽  
2014 ◽  
Vol 160 (11) ◽  
pp. 2387-2395 ◽  
Author(s):  
Hechun Jiang ◽  
Feifei Liu ◽  
Shizhu Zhang ◽  
Ling Lu
Keyword(s):  
Cell Wall ◽  
Plasma Membrane ◽  
Aspergillus Nidulans ◽  
Normal Growth ◽  
Cell Wall Integrity ◽  
Plasma Membrane Atpase ◽  
Growth Defects ◽  
Double Deletion ◽  
Intracellular Ca ◽  
P Type

P-type Ca2+-transporting ATPases are Ca2+ pumps, extruding cytosolic Ca2+ to the extracellular environment or the intracellular Ca2+ store lumens. In budding yeast, Pmr1 (plasma membrane ATPase related), and Pmc1 (plasma membrane calcium-ATPase) cannot be deleted simultaneously for it to survive in standard medium. Here, we deleted two putative Ca2+ pumps, designated AnPmrA and AnPmcA, from Aspergillus nidulans, and obtained the mutants ΔanpmrA and ΔanpmcA, respectively. Then, using ΔanpmrA as the starting strain, the promoter of its anpmcA was replaced with the alcA promoter to secure the mutant ΔanpmrAalcApmcA or its anpmcA was deleted completely to produce the mutant ΔanpmrAΔpmcA. Different from the case in Saccharomyces cerevisiae, double deletion of anpmrA and anpmcA was not lethal in A. nidulans. In addition, deletion of anpmrA and/or anpmcA had produced growth defects, although overexpression of AnPmc1 in ΔanpmrAalcApmcA could not restore the growth defects that resulted from the loss of AnPmrA. Moreover, we found AnPmrA was indispensable for maintenance of normal morphogenesis, especially in low-Ca2+/Mn2+ environments. Thus, our findings suggest AnPmrA and AnPmcA might play important roles in growth, morphogenesis and cell wall integrity in A. nidulans in a different way from that in yeasts.

Receiver operating characteristic (ROC) analysis of neurons in the cat's lateral geniculate nucleus during tonic and burst response mode

1995 ◽  
Vol 12 (4) ◽  
pp. 723-741 ◽  
Author(s):  
W. Guido ◽  
S.-M. Lu ◽  
J.W. Vaughan ◽  
Dwayne W. Godwin ◽  
S. Murray Sherman
Keyword(s):  
Visual Stimulus ◽  
Action Potentials ◽  
Operating Characteristic ◽  
Visual Stimuli ◽  
Roc Curves ◽  
Response Mode ◽  
Burst Mode ◽  
Low Threshold Spike ◽  
Low Threshold ◽  
Roc Area

AbstractRelay cells of the lateral geniculate nucleus respond to visual stimuli in one of two modes: burst and tonic. The burst mode depends on the activation of a voltage-dependent, Ca2+ conductance underlying the low threshold spike. This conductance is inactivated at depolarized membrane potentials, but when activated from hyperpolarized levels, it leads to a large, triangular, nearly all-or-none depolarization. Typically, riding its crest is a high-frequency barrage of action potentials. Low threshold spikes thus provide a nonlinear amplification allowing hyperpolarized relay neurons to respond to depolarizing inputs, including retinal EPSPs. In contrast, the tonic mode is characterized by a steady stream of unitary action potentials that more linearly reflects the visual stimulus. In this study, we tested possible differences in detection between response modes of 103 geniculate neurons by constructing receiver operating characteristic (ROC) curves for responses to visual stimuli (drifting sine-wave gratings and flashing spots). Detectability was determined from the ROC curves by computing the area under each curve, known as the ROC area. Most cells switched between modes during recording, evidently due to small shifts in membrane potential that affected the activation state of the low threshold spike. We found that the more often a cell responded in burst mode, the larger its ROC area. This was true for responses to optimal and nonoptimal visual stimuli, the latter including nonoptimal spatial frequencies and low stimulus contrasts. The larger ROC areas associated with burst mode were due to a reduced spontaneous activity and roughly equivalent level of visually evoked response when compared to tonic mode. We performed a within-cell analysis on a subset of 22 cells that switched modes during recording. Every cell, whether tested with a low contrast or high contrast visual stimulus exhibited a larger ROC area during its burst response mode than during its tonic mode. We conclude that burst responses better support signal detection than do tonic responses. Thus, burst responses, while less linear and perhaps less useful in providing a detailed analysis of visual stimuli, improve target detection. The tonic mode, with its more linear response, seems better suited for signal analysis rather than signal detection.

scholarly journals Novel neuronal and astrocytic mechanisms in thalamocortical loop dynamics

2002 ◽  
Vol 357 (1428) ◽  
pp. 1675-1693 ◽  
Author(s):  
Vincenzo Crunelli ◽  
Kate L. Blethyn ◽  
David W. Cope ◽  
Stuart W. Hughes ◽  
H. Rheinallt Parri ◽  
...  
Keyword(s):  
Low Voltage ◽  
Electrical Coupling ◽  
Low Frequency ◽  
Network Activity ◽  
Thalamic Neuron ◽  
Cellular Mechanisms ◽  
Brain Areas ◽  
Sensory Stimuli ◽  
Loop Dynamics ◽  
Intracellular Ca

In this review, we summarize three sets of findings that have recently been observed in thalamic astrocytes and neurons, and discuss their significance for thalamocortical loop dynamics. (i) A physiologically relevant ‘window’ component of the low–voltage–activated, T–type Ca 2+ current ( I Twindow ) plays an essential part in the slow (less than 1 Hz) sleep oscillation in adult thalamocortical (TC) neurons, indicating that the expression of this fundamental sleep rhythm in these neurons is not a simple reflection of cortical network activity. It is also likely that I Twindow underlies one of the cellular mechanisms enabling TC neurons to produce burst firing in response to novel sensory stimuli. (ii) Both electrophysiological and dye–injection experiments support the existence of gap junction–mediated coupling among young and adult TC neurons. This finding indicates that electrical coupling–mediated synchronization might be implicated in the high and low frequency oscillatory activities expressed by this type of thalamic neuron. (iii) Spontaneous intracellular Ca 2+ ([Ca 2+ ] i ) waves propagating among thalamic astrocytes are able to elicit large and long–lasting N –methyl–D–aspartate–mediated currents in TC neurons. The peculiar developmental profile within the first two postnatal weeks of these astrocytic [Ca 2+ ] i transients and the selective activation of these glutamate receptors point to a role for this astrocyte–to–neuron signalling mechanism in the topographic wiring of the thalamocortical loop. As some of these novel cellular and intracellular properties are not restricted to thalamic astrocytes and neurons, their significance may well apply to (patho)physiological functions of glial and neuronal elements in other brain areas.

Electrophysiology of neurosecretory cells from the pituitary intermediate lobe

1988 ◽  
Vol 139 (1) ◽  
pp. 317-328
Author(s):  
R. N. McBurney ◽  
S. J. Kehl
Keyword(s):  
Cell Cultures ◽  
Calcium Ion ◽  
Action Potentials ◽  
Neurosecretory Cells ◽  
Secretory Process ◽  
High Threshold ◽  
Pars Intermedia ◽  
Low Threshold ◽  
Stimulus Secretion Coupling ◽  
Ca2 Channels

One of the goals in studying the electrical properties of neurosecretory cells is to relate their electrical activity to the process of secretion. A central question in these studies concerns the role of transmembrane calcium ion flux in the initiation of the secretory event. With regard to the secretory process in pituitary cells, several research groups have addressed this question in vitro using mixed primary anterior pituitary cell cultures or clonal cell lines derived from pituitary tumours. Other workers, including ourselves, have used homogeneous cell cultures derived from the pituitary intermediate lobes of rats to examine the characteristics of voltage-dependent conductances, the contribution of these conductances to action potentials and their role in stimulus-secretion coupling. Pars intermedia (PI) cells often fire spontaneous action potentials whose frequency can be modified by the injection of sustained currents through the recording electrode. In quiescent cells action potentials can also be evoked by the injection of depolarizing current stimuli. At around 20 degrees C these action potentials have a duration of about 5 ms. Although most of the inward current during action potentials is carried by sodium ions, a calcium ion component can be demonstrated under abnormal conditions. Voltage-clamp experiments have revealed that the membrane of these cells contains high-threshold, L-type, Ca2+ channels and low-threshold Ca2+ channels. Since hormone release from PI cells appears not to be dependent on action potential activity but does depend on external calcium ions, it is not clear what role these Ca2+ channels play in stimulus-secretion coupling in cells of the pituitary pars intermedia. One possibility is that the low-threshold Ca2+ channels are more important to the secretory process than the high-threshold channels.

FEATURES OF CALCIUM HOMEOSTASIS AND CALCIUM SIGNALING IN NEURONS

Vestnik ◽  
2021 ◽  
pp. 208-214
Author(s):  
Б.К. Кайрат ◽  
С.Т. Тулеуханов ◽  
В.П. Зинченко
Keyword(s):  
Plasma Membrane ◽  
Calcium Signaling ◽  
Calcium Binding ◽  
Intracellular Signaling ◽  
Cell Damage ◽  
Compensatory Mechanisms ◽  
Physiological Processes ◽  
Intracellular Ca ◽  
Ca Ions ◽  
Ca Homeostasis

Ионы Са являются основным мессенджером в регуляции физиологических функций клеток. Внутриклеточном пространстве ионы Ca могут свободно состоянии диффундироваться в различных частях цитоплазмы, в то же время значительное количество Ca в связанном виде накапливается в различных внутриклеточных депо или в составе кальций-связывающих белков. Регуляция физиологических процессов с ионами внутриклеточного Са происходит в диапазоне концентраций 10 М, тогда как концентрация Са во внеклеточном пространстве выше и составляет 10 М, для поддержании градиента концентраций в клетках имеются важные Са транспортирующие системы плазматической мембраны, эндоплазматического ретикулума и митохондрий. В нейронах функционируют внутриклеточные ферменты и белки плазматической мембраны для поддержания Са-гомеостаза и реализации механизмов внутриклеточной сигнализации для обеспечения жизнедеятельности в выживании клеток. Нарушение или гиперактивация одного или нескольких механизмов кальциевой сигнализации может привести к повреждению и гибели нейронов в случае отсутствия компенсаторных механизмов. Ca ions are a key messenger for the regulation of most of the physiological functions of cells. Inside the cell, Ca ions can freely diffuse in various parts of the cytoplasm, but a significant amount of Ca is also bound in various intracellular depots or in the form of calcium-binding proteins. The regulation of physiological processes by intracellular Ca ions occurs in the concentration range of 10 M, and the concentration of Ca in the extracellular space is higher and is 10 M, and to maintain this concentration gradient, cells have Ca-transporting systems of the plasma membrane, endoplasmic reticulum and mitochondria. In neurons, a large number of intracellular enzymes and plasma membrane proteins function to maintain Ca-homeostasis and implement intracellular signaling mechanisms to ensure vital activity in the survival of cells. Violation or hyperactivation of one or more mechanisms of calcium signaling can lead to cell damage and death in the absence of compensatory mechanisms.

ADP-ribose gates the fertilization channel in ascidian oocytes

1998 ◽  
Vol 275 (5) ◽  
pp. C1277-C1283 ◽  
Author(s):  
Martin Wilding ◽  
Gian Luigi Russo ◽  
Anthony Galione ◽  
Marcella Marino ◽  
Brian Dale
Keyword(s):  
Plasma Membrane ◽  
Ion Channel ◽  
Reversal Potential ◽  
Ciona Intestinalis ◽  
Second Messenger ◽  
Tetraacetic Acid ◽  
Independent Manner ◽  
Unitary Conductance ◽  
Intracellular Ca ◽  
Hydrolysis Of

We report an ion channel in the plasma membrane of unfertilized oocytes of the ascidian Ciona intestinalis that is directly gated by the second messenger ADP-ribose. The ion channel is permeable to Ca2+ and Na+ and is characterized by a reversal potential between 0 and +20 mV and a unitary conductance of 140 pS. Preinjection of the Ca2+ chelator 1,2-bis(2-aminophenoxy)ethane- N, N, N′, N′-tetraacetic acid (BAPTA) or antagonists of intracellular Ca2+ release channels into oocytes did not inhibit the ADP-ribose current, demonstrating that the channel is activated in a Ca2+-independent manner. Both the fertilization current and the current induced by the injection of nicotinamide nucleotides are blocked by nicotinamide, suggesting that the ADP-ribose channel is activated at fertilization in a nicotinamide-sensitive manner. These data suggest that ascidian sperm trigger the hydrolysis of nicotinamide nucleotides in the oocyte to ADP-ribose and that this mechanism is responsible for the production of the fertilization current.

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