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.

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.

scholarly journals Role of Intrinsic Properties in Drosophila Motoneuron Recruitment During Fictive Crawling

2010 ◽  
Vol 104 (3) ◽  
pp. 1257-1266 ◽  
Author(s):  
Jennifer E. Schaefer ◽  
Jason W. Worrell ◽  
Richard B. Levine
Keyword(s):  
Resting Membrane Potential ◽  
High Threshold ◽  
Intrinsic Properties ◽  
Whole Cell ◽  
Whole Cell Patch Clamp ◽  
Drosophila Larvae ◽  
Low Threshold ◽  
Evoked Activity

Motoneurons in most organisms conserve a division into low-threshold and high-threshold types that are responsible for generating powerful and precise movements. Drosophila 1b and 1s motoneurons may be analogous to low-threshold and high-threshold neurons, respectively, based on data obtained at the neuromuscular junction, although there is little information available on intrinsic properties or recruitment during behavior. Therefore in situ whole cell patch-clamp recordings were used to compare parameters of 1b and 1s motoneurons in Drosophila larvae. We find that resting membrane potential, voltage threshold, and delay-to-spike distinguish 1b from 1s motoneurons. The longer delay-to-spike in 1s motoneurons is a result of the shal-encoded A-type K+ current. Functional differences between 1b and 1s motoneurons are behaviorally relevant because a higher threshold and longer delay-to-spike are observed in MNISN-1s in pairwise whole cell recordings of synaptically evoked activity during bouts of fictive locomotion.

scholarly journals Modulation of Recombinant Human T-type calcium Channels by Δ9-tetrahydrocannabinolic acid in vitro

2020 ◽  
Author(s):  
Somayeh Mirlohi ◽  
Chris Bladen ◽  
Marina Santiago ◽  
Mark Connor
Keyword(s):  
Calcium Channels ◽  
Low Voltage ◽  
Absence Epilepsy ◽  
Resting Membrane Potential ◽  
Peak Current ◽  
Negative Shift ◽  
Whole Cell Patch Clamp ◽  
Psychoactive Effects ◽  
Steady State Inactivation

AbstractIntroductionLow voltage-activated T-type calcium channels (T-type ICa), CaV3.1, CaV3.2, and CaV3.3 are opened by small depolarizations from the resting membrane potential in many cells and have been associated with neurological disorders including absence epilepsy and pain. Δ9-tetrahydrocannabinol (THC) is the principal psychoactive compound in Cannabis and also directly modulates T-type ICa, however, there is no information about functional activity of most phytocannabinoids on T-type calcium channels, including Δ9-tetrahydrocannabinol acid (THCA), the natural non-psychoactive precursor of THC. The aim of this work was to characterize THCA effects on T-type calcium channels.Materials and MethodsWe used HEK293 Flp-In-TREx cells stably expressing CaV3.1, 3.2 or 3.3. Whole-cell patch clamp recordings were made to investigate cannabinoid modulation of ICa.ResultsTHCA and THC inhibited the peak current amplitude CaV3.1 with a pEC50s of 6.0 ± 0.7 and 5.6 ± 0.4, respectively. 1μM THCA or THC produced a significant negative shift in half activation and inactivation of CaV3.1 and both drugs prolonged CaV3.1 deactivation kinetics. THCA (10 μM) inhibited CaV3.2 by 53% ± 4 and both THCA and THC produced a substantial negative shift in the voltage for half inactivation and modest negative shift in half activation of CaV3.2. THC prolonged the deactivation time of CaV3.2 while THCA did not. THCA inhibited the peak current of CaV3.3 by 43% ± 2 (10μM) but did not notably affect CaV3.3 channel activation or inactivation, however, THC caused significant hyperpolarizing shift in CaV3.3 steady state inactivation.DiscussionTHCA modulated T-type ICa currents in vitro, with significant modulation of kinetics and voltage dependence at low μM concentrations. This study suggests that THCA may have potential for therapeutic use in pain and epilepsy via T-type channel modulation without the unwanted psychoactive effects associated with THC.

scholarly journals Monitoring and Modulating Inflammation-Associated Alterations in Synaptic Plasticity: Role of Brain Stimulation and the Blood–Brain Interface

Biomolecules ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 359
Author(s):  
Maximilian Lenz ◽  
Amelie Eichler ◽  
Andreas Vlachos
Keyword(s):  
Synaptic Plasticity ◽  
Brain Stimulation ◽  
Vascular Function ◽  
Neuropsychiatric Symptoms ◽  
Systemic Infection ◽  
Brain Functions ◽  
Blood Brain ◽  
Brain Interface ◽  
The Central Nervous System

Inflammation of the central nervous system can be triggered by endogenous and exogenous stimuli such as local or systemic infection, trauma, and stroke. In addition to neurodegeneration and cell death, alterations in physiological brain functions are often associated with neuroinflammation. Robust experimental evidence has demonstrated that inflammatory cytokines affect the ability of neurons to express plasticity. It has been well-established that inflammation-associated alterations in synaptic plasticity contribute to the development of neuropsychiatric symptoms. Nevertheless, diagnostic approaches and interventional strategies to restore inflammatory deficits in synaptic plasticity are limited. Here, we review recent findings on inflammation-associated alterations in synaptic plasticity and the potential role of the blood–brain interface, i.e., the blood–brain barrier, in modulating synaptic plasticity. Based on recent findings indicating that brain stimulation promotes plasticity and modulates vascular function, we argue that clinically employed non-invasive brain stimulation techniques, such as transcranial magnetic stimulation, could be used for monitoring and modulating inflammation-induced alterations in synaptic plasticity.

Effect of low chloride on relaxation in hamster diaphragm muscle

1986 ◽  
Vol 61 (1) ◽  
pp. 180-184 ◽  
Author(s):  
S. A. Esau ◽  
N. Sperelakis
Keyword(s):  
Membrane Potential ◽  
Muscle Fatigue ◽  
Time Constant ◽  
Diaphragm Muscle ◽  
Resting Membrane Potential ◽  
Krebs Solution ◽  
Sarcolemmal Membrane ◽  
Cl Conductance

With muscle fatigue the chloride (Cl-) conductance of the sarcolemmal membrane decreases. The role of lowered Cl- conductance in the prolongation of relaxation seen with fatigue was studied in isolated hamster diaphragm strips. The muscles were studied in either a Krebs solution or a low Cl- solution in which half of the NaCl was replaced by Na-gluconate. Short tetanic contractions were produced by a 160-ms train of 0.2-ms pulses at 60 Hz from which tension (T) and the time constant of relaxation were measured. Resting membrane potential (Em) was measured using KCl-filled microelectrodes with resistances of 15–20 M omega. Mild fatigue (20% fall in tension) was induced by 24–25 tetanic contractions at the rate of 2/s. There was no difference in Em or T in the two solutions, either initially or with fatigue. The time constant of relaxation was greater in low Cl- solution, both initially (22 +/- 3 vs. 18 +/- 5 ms, mean +/- SD, P less than 0.05) and with fatigue (51 +/- 18 vs. 26 +/- 7 ms, P less than 0.005). Lowering of sarcolemmal membrane Cl- conductance appears to play a role in the slowing of relaxation of hamster diaphragm muscle seen with fatigue.

Role of neurotransmitter release and cyclic AMP-dependent membrane phosphorylation in low voltage myocardial automaticity

1981 ◽  
Vol 37 (7) ◽  
pp. 731-734 ◽  
Author(s):  
M. E. Saxon ◽  
V. G. Safronova ◽  
A. V. Lazarev ◽  
A. A. Freidin ◽  
Y. M. Kokoz
Keyword(s):  
Cyclic Amp ◽  
Neurotransmitter Release ◽  
Low Voltage ◽  
Membrane Phosphorylation

scholarly journals Primary care and the early phases of schizophrenia in the Czech Republic

2010 ◽  
Vol 19 (3) ◽  
pp. 243-250
Author(s):  
David Holub ◽  
Barbora Wenigová ◽  
Daniel Umbricht ◽  
Andor E. Simon
Keyword(s):  
Primary Care ◽  
Czech Republic ◽  
Warning Signs ◽  
Outpatient Services ◽  
The Czech Republic ◽  
Mental Health Reforms ◽  
Low Threshold ◽  
The City ◽  
Early Phases

SUMMARYAim– To explore knowledge, treatment setting, attitudes and needs associated with patients in early phases of psychosis among general practitioners (GPs) in Prague, andto compare results with GPs from 6 countries participating in theInternational GP Study(IGPS)on Early Psychosis(Canada, Australia, New Zealand, England, Norway,Austria).Methods– Survey questionnaires were mailed to 648 GPs in the city of Prague.Results– The response rate was 19.9%. Prague GPs showed significantly lower diagnostic knowledge of early phases of psychosis compared to their international colleagues. They frequently indicated depression/anxiety and somatic complaints as early warnings of psychosis. They more often considered their behaviour to be problematic and more commonly handed them over to specialists. The majority of Prague GPs wished specialized outpatient services for low-threshold referrals of such patients.Conclusions– Along the mental health reforms in the Czech Republic which emphasis the role of primary care, GPs' knowledge of the early warning signs of psychosis needs to be improved.Declaration of Interest:The study was supported by an unrestricted grant from Sanofi-Synthélabo SA, Switzerland, to the principal investigators of the IGPS (AES, DU). The authors have stated that there are none; all authors are independent from the funding body and the views expressed in this paper have not been influenced by the funding source.

The role of K-channels in the formation of a nociceptive signal in the rat trigeminal nerve

2021 ◽  
Author(s):  
A.D. Buglinina ◽  
T.M. Verkhoturova ◽  
O.Sh. Gafurov ◽  
K.S. Koroleva ◽  
G.F. Sitdikova
Keyword(s):  
Key Words ◽  
Trigeminal Nerve ◽  
Key Words Migraine ◽  
K Channels ◽  
Kv Channel ◽  
Inflammatory Agent ◽  
Kv Channels ◽  
Pain Signal ◽  
Isolated Rat

The central problem of this work is to elucidate the mechanisms of pain in migraine and to establish the role of Kv channels in regulating the excitability of meningeal afferents of the trigeminal nerve that form a pain signal in migraine. The study was conducted on a preparation of an isolated rat skull. It was found that Kv-channel inhibitors 4-aminopyridine (100 microns and 1 mM) and tetraethylammonium (5mm) lead to an increase in the excitability of trigeminal nerve afferents, at the same time, this effect was partially removed by a nonsteroidal anti–inflammatory agent - naproxen, and was not sensitive to sumatriptan, a classic anti-migraine drug. Key words: migraine, K-channels, trigeminal nerve, 4-aminopyridine, tetraethylammonium, naproxen, sumatriptan.

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