Overview of Ion Channels, Antiepileptic Drugs, and Seizures
Carl L. Faingold, Gerhard H. Fromm in Drugs for Control of Epilepsy:, 2019
Potassium channels are ubiquitous in eukaryotic cells and exhibit more diverse characteristics than channels for other ions.22 Over a dozen types of K+ channels have already been identified using variations on the patch clamp technique.2 Selective toxins also have been discovered that potently block particular types of K+ channels, which allow examination of the role of the particular current type in controlling the excitability pattern of specific cell types.23 These agents include apamin, a toxin from the honey bee, that inhibits Ca2+-activated K+ channels. Two scorpion toxins, charybdotoxin and noxioustoxin, and a toxin from mamba snake venom, dendrotoxin, also selectively affect different K+ channels.23 G-proteins act to couple many types of K+ channel to neurotransmitters.24
Helping You Understand Dr. Goldstein's Book
Katie Courmel in A Companion Volume to Dr. Jay A. Goldstein's Betrayal by the Brain, 2013
Tacrine is a centrally acting cholinesterase inhibitor that increases the levels of ACh in the brain. Tacrine is a potassium channel blocker, and it also blocks voltage-gated sodium and calcium channels. The function of potassium channels in neurosomatic disorders is still unclear, but they do modulate cellular excitability. K channel blockers act by keeping potassium confined to intracellular regions, depolarizing cell membranes, increasing "membrane potential" to excite the cell, and stimulating the release of neurotransmitters. Tacrine also blocks NMDA receptor channels in the open state, perhaps enhancing the effect of glutamate acting at the NMDA receptor or allowing calcium ions to flow through the channel enhancing synaptic transmission. In rat studies, tacrine enhances NO synthase activity in the hippocampus—a finding that may be relevant to humans, given the role of NO in mediating the NMDA receptor to enhance synaptic transmission for long-term potentiation. See section on GLUTAMATE for more information about this process.
Molecular Mechanisms of Nociception
Gary W. Jay in Chronic Pain, 2007
Potassium channels appear to play an important role in the development of neuronal excitability. There are four families of potassium channels that have different structures, neuropharmacological sensitivities, and functional characteristics: the voltage-gated (KV), calcium activated [K (Ca)], inward rectifier [K (ir)], and the two-pore channels [K (2P)] K (+) (80). Antinociception has been associated with the opening of some forms of these K (+) channels induced by agonists of multiple G-protein coupled receptors, including alpha(2)-adrenoceptors, opioid, GABA(B), muscarinic, serotonin 5HT-1A, nonsteroidal anti inflammatory drugs (NSAIDs), tricyclic antidepressants, and cannabinoid receptors (80). New research indicates that drugs that directly open K (+) channels produce antinociceptive effects in various models of acute and chronic pain (80).
Hyperosmolar Potassium Inhibits Corneal Myofibroblast Transformation and Prevent Corneal Scar
Published in Current Eye Research, 2023
Kai Liao, Zekai Cui, Zhijie Wang, Yu Peng, Shibo Tang, Jiansu Chen
Besides, several studies have found a close relationship between the potassium channels and fibrotic diseases. Nattel et al. showed that fibroblast KCNJ2 expression and currents are upregulated in congestive heart failure, thereby hyperpolarizing resting membrane potential and enhancing atrial fibroblast proliferation.35 Bradding et al. demonstrated that the potassium channel K(Ca)3.1 plays a crucial role in human fibrocyte migration.36 Moreover, K(Ca)3.1 inhibitor has been documented to significantly attenuate corneal fibrosis in cell culture.37 Accordingly, we hypothesize that hyperosmolar potassium could affect the function of the potassium channel in CFs, and hence, inhibit cell fibrosis. Further studies are needed to explore the mechanisms underlying the antifibrotic function of potassium.
Supraventricular tachycardia with the use of phentermine: case report and review of literature
Published in Postgraduate Medicine, 2021
Sundeep Kumar, Akhil Mogalapalli, Ruthvik Srinivasamurthy, Sayed T. Hussain, Philip L. Mar
Other documented adverse effects of phentermine include pulmonary arterial hypertension and valvular disease when phentermine was used along with fenfluramine [16]. This combination was later withdrawn from the market [16]. The possible mechanism between phentermine and amphetamine derivatives causing cardiac toxicity is likely to be multifactorial. The primary mechanism seems to be due to the sympathomimetic properties of phentermine. However, apart from heart rate elevation and increased ectopic activity, other deleterious effects have been reported. As shown, chronic exposure to sympathomimetic drugs can result in myocardial degeneration, necrosis, and fibrosis [17]. A secondary mechanism of cardiac toxicity could be due to hypoxia and chronic ischemia secondary to coronary artery vasospasm [11,12]. Atrial fibrosis has been shown to act as a substrate for development of supraventricular arrhythmias by reentry phenomenon or increased cardiac myocyte automaticity [18]. Others have shown that scar formation following ablations for atrial fibrillation has specifically increased the incidence of AVNRT requiring slow pathway modification [19]. Amphetamine has also been shown to affect the cardiac action potential by blocking the transient outward potassium channel. The transient outward potassium channel controls the majority of repolarization phase during the cardiac action potential. Hence, amphetamines blocking this channel could potentially enhance AV nodal conduction resulting in increased arrhythmias [20].
Ketogenic diet: overview, types, and possible anti-seizure mechanisms
Published in Nutritional Neuroscience, 2021
Mohammad Barzegar, Mohammadreza Afghan, Vahid Tarmahi, Meysam Behtari, Soroor Rahimi Khamaneh, Sina Raeisi
Two-pore domain potassium (K2P) channels, also known as potassium leak channels, are a major and distinct subclass of the potassium channel superfamily. They have been discovered in a wide variety of mammalian cells including neurons, myocytes, glia, and many different types of epithelial cells. These channels are structurally different from most other classes of potassium channels which form a functional tetramer. It has been shown that each subunit of K2P channels has two pore-forming regions and four trans-membrane segments, and thus, they form functional dimers. Functionally, these channels are spontaneously active leading to continuous efflux of potassium ions through the cell membrane which is necessary for setting a hyperpolarized resting potential of the cell membrane. Therefore, K2P channels may directly influence the duration and frequency of action potential firings [56,58–60]. These channels can be also modulated by a variety of physical, chemical and natural factors including voltage, temperature, mechanical pressure, protons (pH), and volatile anesthetics. It has been suggested that K2P channels may also be activated by ketone bodies and certain fatty acids as well [59,61]. Thus, KD-induced raises in blood ketone bodies and fatty acids as well may regulate neuron membrane excitability by activating K2P channels, and this can be assumed as another probable anticonvulsant mechanism of KD.