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
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).
The Opioid Epidemic
Sahar Swidan, Matthew Bennett in Advanced Therapeutics in Pain Medicine, 2020
Opioid receptors are G protein-coupled receptors (GPCR) with seven transmembrane helical loops—three intracellular loops and three extracellular loops. The extracellular loops contain the pocket in which the signaling molecules bind. Acute stimulation of the receptor results in activation of the G-protein and a blocking of the voltage-gated dependent calcium channel which prevents the flow of calcium into the neurons. A potassium channel is also activated—pumping K+ ions out of the neuron. The result is hyperpolarization, activation of components of the mitogen-activated proteins (MAP) kinase cascade, and a decrease in neurotransmitter release such as glutamate and substance P.1 Ultimately analgesia results.
Mechano-gated channels in C. elegans
Published in Journal of Neurogenetics, 2020
Umar Al-Sheikh, Lijun Kang
Evolutionary genetics revealed that potassium channels are widely expressed archaic ion channels across species. Potassium channels control the influx and efflux of K+ ions through cell membranes (Douguet & Honore, 2019). The opposing polarization and depolarization of potassium versus calcium and sodium channels promote membrane potential/cell excitability for numerous vital cellular mechanics as well as survival. To date, four main classes of potassium channels are known—Calcium-activated (Kca), Inward rectifying (Kir), Tandem/two pore domain (K2P) and voltage-gated potassium channels (KV). Previously known as K+ background (leak) channels, K2P channel subunits are encoded by 15 KCNK mammalian genes, 11 Drosophila genes and 50 putative C. elegans genes. Out of the four potassium ion channels, only two K2P subfamilies—Tandem pore domain in weak rectifying K+ channel (TWIK) and TWIK-related K+ channel (TREK) have been divulged as mechano-gated channels. Thus far, TREK1 (KCNK2), TREK2 (KCNK10) and TRAAK (TWIK-related arachidonic acid-stimulated K+) channels have been found to be mechano-gated channels in mammals (Chalfie, 2009) but there is yet no mechanically activated K2P channel exposed in C. elegans.
Potassium channels as prominent targets and tools for the treatment of epilepsy
Published in Expert Opinion on Therapeutic Targets, 2021
ES Nikitin, LV Vinogradova
Most potassium channels are gated by transmembrane voltage, intracellular Ca2+, and several physiological mediators such as G-proteins. The role of K+ in membrane physiology has been extensively studied in rodent models as basic electrophysiological properties and bursting patterns of primate central neurons are generally similar to those reported for the rodent [30]. Most attention is usually paid to pyramidal neurons, as they are the most numerous in the cortex (~80% of all neurons). The experimentally identified reversal potential of K+ in neocortical neurons (rodent brain slice, layer 5) is ~ −93 mV, while their resting potentials are about – 80 mV [11]. According to the Hodgkin–Huxley theory, the opening of K+ channels during the action potential produces a negative shift of the transmembrane potential to repolarize the neuron (Figure 2b-c). Thus, K+ currents reduce neuronal excitability immediately after each action potential.
Non-thermal membrane effects of electromagnetic fields and therapeutic applications in oncology
Published in International Journal of Hyperthermia, 2021
Peter Wust, Ulrike Stein, Pirus Ghadjar
We assume that every channel act like a diode because ions can only be directed along the electrochemical gradient. Our example (Figure 4) shows a huge Ca2+ gradient between the extracellular concentration of 1.3 mmol/l and intracellular concentration of only 100 nmol/L (>10,000-fold). Then, the equilibrium (Nernst) potential for Ca2+ is UCa ≈ 250 mV, which is far from the typical membrane potential of –60 mV. This electrochemical gradient is enormous, causing a strong tendency for calcium influx and intracellular calcium overload if the calcium channel is open. Instead, in the case of potassium, the K+ equilibrium (Nernst) potential of UK = –95 mV is below the membrane potential of 60 mV. Therefore, K+ ions flow from intracellular to extracellular to bring the membrane potential nearer to the K+ equilibrium potential. Thus, a potassium channel acts like a diode with the forward direction from intra- to extracellular.