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Antiepileptic Drugs
Published in Sahab Uddin, Rashid Mamunur, Advances in Neuropharmacology, 2020
Absence seizures are associated with activation of T-type calcium channels (Fuentealba et al., 2004; Song et al., 2004). T-type calcium channels are active only when the cell is hyperpolarized. During the awake state, hyperpolarization of thalamic neurons is mediated by various mechanisms like an increase in inhibitory input from the reticular nucleus mediated by GABA neurotransmitter, increase in intracellular potassium, or a loss of excitatory neurotransmission mediated by glutamate and NMDA receptors (Ulrich and Huguenard, 1997; Sohal and Huguenard, 2003). Hyperpolarization results in activation of T-type calcium channels in thalamic relay as well as reticular neurons, resulting in synchronous depolarization of neurons in cerebral cortex via excitatory thalamocortical connections (Song et al., 2004). This activity of the T-type calcium channel in the relay neurons results in generation of 3-per-second spike-and-wave activity, characteristic of absence seizures. Thalamocortical rebound spikes result from inputs from cortical and reticular neurons. A large fraction of thalamocortical neurons cannot fire, resulting in disruption of information flow to cortex resulting in absence of phenotypic manifestation (Khosravani and Zamponi, 2006). The graphic representation of the above mechanism is depicted in Figure 14.3.
The heart
Published in Laurie K. McCorry, Martin M. Zdanowicz, Cynthia Y. Gonnella, Essentials of Human Physiology and Pathophysiology for Pharmacy and Allied Health, 2019
Laurie K. McCorry, Martin M. Zdanowicz, Cynthia Y. Gonnella
The “resting” membrane potential, or pacemaker potential, is different from that of neurons, which were discussed in Chapter 3 (Membrane Potential). First, this potential is approximately −55 mV, which is less negative than that found in neurons (−70 mV) (see Figure 7.3; panel A). Secondly, the pacemaker potential is unstable and slowly depolarizes toward threshold (Phase 4). Three important ion currents contribute to this slow depolarization and involve the following types of channels: Potassium channelsF-type sodium channelsT-type calcium channels
Didi
Published in Walter J. Hendelman, Peter Humphreys, Christopher R. Skinner, The Integrated Nervous System, 2017
Walter J. Hendelman, Peter Humphreys, Christopher R. Skinner
Inhibition of T-type calcium channels: T-type Ca++ channels are particularly prominent in neurons located in the non-specific (reticular) thalamic nuclei. Inhibition of these channels appears to suppress generalized corticoreticular epileptogenic mechanisms, particularly in the case of absence seizures, rather than generalized tonic-clonic seizures. Ethosuximide is an anti-epileptic drug that has its main effect through this mechanism.
An antihypertensive agent benidipine is an effective neuroprotective and antiepileptic agent: an experimental rat study
Published in Neurological Research, 2021
Mehmet Nuri Koçak, Remzi Arslan, Abdulmecit Albayrak, Erdal Tekin, Mustafa Bayraktar, Muhammet Çelik, Zülküf Kaya, Hüseyin Bekmez, Taha Tavaci
In another cell culture study, Nikonenko I et al. were investigated the efficacy of T-type calcium channel blockade to prevent cell death from delayed ischemic injury and found that many T-type calcium blocking agents were protective against cell death [32]. However, benidipine was not among the agents studied. Benjamin J. Kopecky et al. complied a review on investigating whether T-type calcium channel blockers are neuroprotective or not [33]. As a result of this review, the authors stated that there was many T-type calcium channel blockers, they do not only provide neuroprotection as a result of specific T-type channel inhibition, but possibly also through other channels and pathways. They stated that benidipine, as one of these active substances, is not known whether it performs neuroprotection or not.
Up-regulation of Cav3.1 expression in SH-SY5Y cells induced by lidocaine hydrochloride
Published in Artificial Cells, Nanomedicine, and Biotechnology, 2018
Qin Gong, Xianjie Wen, Heng Li, Jian He, Yunhua Wang, Huiping Wu, Hanbing Wang, Xiaoping Wang
One important role of the voltage-gated Ca2 + channel (VGCC) is the regulation of the electrical excitability of the neurons. They regulate the intracellular Ca2 + concentration and play a key role in neuronal physiology. According with the activation voltage, VGCCs are divided into high-voltage-activated (HVA) Ca2 + channel and low-voltage-activated (LVA) calcium channel. T-type calcium channel, belonging to the low-voltage-activated calcium channel, is divided into Cav3.1, Cav3.2 and Cav3.3 [8]. T-type calcium channels can be activated at resting membrane potentials and calcium ion enters into intracellular by the T-type calcium channel. As well as, there is a window current (overlap between the activated and inactivated membrane potentials) for the T-type calcium channel which resulted in the calcium ion influx through the open T-type calcium channel at the resting membrane potential [9]. T-type calcium channel plays an important role in the regulation of the neurons excitability [10]. The neurotoxicity of the local anaesthetics causes neurons injury resulting in the changes of the excitability. Consequently, we deduce that the neurons excitability changes induced by local anaesthetics may be involved with the T-type calcium channel.
Synthesis and biological evaluation of pyrrolidine-based T-type calcium channel inhibitors for the treatment of neuropathic pain
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2018
Hak Kyun Yang, Woo Seung Son, Keon Seung Lim, Gun Hee Kim, Eun Jeong Lim, Changdev G. Gadhe, Jae Yeol Lee, Kyu-Sung Jeong, Sang Min Lim, Ae Nim Pae
One of the encouraging strategies to treat neuropathic pain is modulation of intracellular calcium levels8,9 either directly by controlling voltage-gated calcium channels or indirectly by regulating receptors such as nicotinic acetylcholine receptors10,11. Among several voltage-gated calcium channels, T-type calcium channels have received great attention as one of the promising molecular targets for neuropathic pain12,13. These are low voltage-activated (LVA) channels composed of α1 subunit single pore, and three isoforms of T-type calcium channels have been identified14: Cav3.1 (α1G)15, Cav3.2 (α1H)16, Cav3.3 (α1I)17. In contrast to high voltage-activated (HVA) channels, T-type calcium channels are activated even after a slight depolarisation of the cell membrane, functioning at near-resting membrane potentials18. Due to this unique voltage sensitivity, T-type calcium channels can regulate neuronal excitability and oscillatory behaviour19.