Levosimendan exerts anticonvulsant properties against PTZ-induced seizures in mice through activation of nNOS/NO pathway: Role for KATP channel

Gooshe, Maziar; Tabaeizadeh, Mohammad; Aleyasin, Ali Reza; Mojahedi, Payam; Ghasemi, Keyvan; Yousefi, Farbod; Vafaei, Ali; Amini-Khoei, Hossein; Amiri, Shayan; Dehpour, Ahmad Reza

doi:10.1016/j.lfs.2016.11.006

Cited by 17 publications

(15 citation statements)

References 53 publications

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“…Moreover, a number of drugs that display anticonvulsant properties in animal models may exert their effects through K ATP channels. Examples include the inotropic calcium sensitizers levosimendan (183), glycolytic inhibitor 2-deoxy-D-glucose (594), K + -sparing diuretic riamterene (594), hypnotic agent zolpidem (469) and fatty acid caprylic acid (472) though the mechanisms are complex and mostly seem to be indirect in nature. Another interesting example is the anticonvulsant and analgesic gabapentin which decreases [3H]noradrenaline release from rat hippocampal and human neocortical slices.…”

Section: Miscellaneous Agentsmentioning

confidence: 99%

ATP‐Sensitive Potassium Channels and Their Physiological and Pathophysiological Roles

Tinker

Aziz

et al. 2018

Comprehensive Physiology

111

112

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ATP sensitive potassium channels (K ) are so named because they open as cellular ATP levels fall. This leads to membrane hyperpolarization and thus links cellular metabolism to membrane excitability. They also respond to MgADP and are regulated by a number of cell signaling pathways. They have a rich and diverse pharmacology with a number of agents acting as specific inhibitors and activators. K channels are formed of pore-forming subunits, Kir6.1 and Kir6.2, and a large auxiliary subunit, the sulfonylurea receptor (SUR1, SUR2A, and SUR2B). The Kir6.0 subunits are a member of the inwardly rectifying family of potassium channels and the sulfonylurea receptor is part of the ATP-binding cassette family of proteins. Four SURs and four Kir6.x form an octameric channel complex and the association of a particular SUR with a specific Kir6.x subunit constitutes the K current in a particular tissue. A combination of mutagenesis work combined with structural studies has identified how these channels work as molecular machines. They have a variety of physiological roles including controlling the release of insulin from pancreatic β cells and regulating blood vessel tone and blood pressure. Furthermore, mutations in the genes underlie human diseases such as congenital diabetes and hyperinsulinism. Additionally, opening of these channels is protective in a number of pathological conditions such as myocardial ischemia and stroke. © 2018 American Physiological Society. Compr Physiol 8:1463-1511, 2018.

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Section: Miscellaneous Agentsmentioning

confidence: 99%

ATP‐Sensitive Potassium Channels and Their Physiological and Pathophysiological Roles

Tinker

Aziz

et al. 2018

Comprehensive Physiology

111

112

View full text Add to dashboard Cite

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“…We found two reports that support this hypothesis. One notes that KATP channel opening by levosimendan may activate nNOS and thereby generate NO in the hippocampus and temporal cortex [49]. Another report indicates that vasodilatation caused by KATP channel opening by minoxidil was inhibited by L-NAME in rat renal vascular smooth muscles [50].…”

Section: Katp Channel Openers and No Productionmentioning

confidence: 99%

Cardiac Na+/Ca2+ exchange stimulators among cardioprotective drugs

Watanabe

2019

J Physiol Sci

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We previously reviewed our study of the pharmacological properties of cardiac Na + /Ca 2+ exchange (NCX1) inhibitors among cardioprotective drugs, such as amiodarone, bepridil, dronedarone, cibenzoline, azimilide, aprindine, and benzyl-oxyphenyl derivatives (Watanabe et al. in J Pharmacol Sci 102:7-16, 2006). Since then we have continued our studies further and found that some cardioprotective drugs are NCX1 stimulators. Cardiac Na + /Ca 2+ exchange current (I NCX1) was stimulated by nicorandil (a hybrid ATP-sensitive K + channel opener), pinacidil (a non-selective ATP-sensitive K + channel opener), flecainide (an antiarrhythmic drug), and sodium nitroprusside (SNP) (an NO donor). Sildenafil (a phosphodiesterase-5 inhibitor) further increased the pinacidil-induced augmentation of I NCX1. In paper, here I review the NCX stimulants that enhance NCX function among the cardioprotective agents we examined such as nicorandil, pinacidil, SNP, sildenafil and flecainide, in addition to atrial natriuretic (ANP) and dofetilide, which were reported by other investigators. Keywords Cardiac Na + /Ca 2+ exchanger (NCX1) • Cardiac Na + /Ca 2+ exchange current (I NCX1) • NCX1 stimulator • Patchclamp method • Cardioprotective drug

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“…-Scully et al, 2007;Krill and Dawson-Scully, 2016). Convincing evidence exists that links multiple families of K + channels that reduce neuronal excitability when K + conductance is increased in invertebrate and mammalian models (Kuebler et al, 2001;Li et al, 2017;Wang et al, 2015;Boddum et al, 2017;Gooshe et al, 2017;Whitmire et al, 2017). One study investigated the role of a K ATP channel, Kir6.2, in mice lacking BAD, a protein involved in glucose metabolism.…”

Section: Discussionmentioning

confidence: 99%

Contribution of a natural polymorphism, protein kinase G, modulates electroconvulsive seizure recovery in D. melanogaster

Kelly

Risley

Miranda

2018

Journal of Experimental Biology

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is a well-characterized model for neurological disorders and is widely used for investigating causes of altered neuronal excitability leading to seizure-like behavior. One method used to analyze behavioral output of neuronal perturbance is recording the time to locomotor recovery from an electroconvulsive shock. Based on this behavior, we sought to quantify seizure susceptibility in larval with differences in the enzymatic activity levels of a major protein, cGMP-dependent protein kinase (PKG). PKG, encoded by, has two natural allelic variants and has previously been implicated in several important physiological characteristics including: foraging patterns, learning and memory, and environmental stress tolerance. The well-established NO/cGMP/PKG signaling pathway found in the fly, which potentially targets downstream K channel(s), ultimately impacts membrane excitability, leading to our hypothesis: altering PKG enzymatic activity modulates time to recovery from an electroconvulsive seizure. Our results show that by both genetically and pharmacologically increasing PKG enzymatic activity, we can decrease the locomotor recovery time from an electroconvulsive seizure in larval .

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Levosimendan exerts anticonvulsant properties against PTZ-induced seizures in mice through activation of nNOS/NO pathway: Role for KATP channel

Cited by 17 publications

References 53 publications

ATP‐Sensitive Potassium Channels and Their Physiological and Pathophysiological Roles

ATP‐Sensitive Potassium Channels and Their Physiological and Pathophysiological Roles

Cardiac Na+/Ca2+ exchange stimulators among cardioprotective drugs

Contribution of a natural polymorphism, protein kinase G, modulates electroconvulsive seizure recovery in D. melanogaster

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