Na+ channel block prevents the ischemia-induced release of norepinephrine from spinal cord slices

Uchihashi, Yoshitaka; Bencsics, Agnes; Umeda, Eiichiro; Nakai, Tetsuji; Sato, Tetsuo; Vizi, E. Sylvester

doi:10.1016/s0014-2999(98)00049-1

Cited by 25 publications

(15 citation statements)

References 41 publications

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“…TTX) in caudate nucleus slices. In spinal cord slices, ischaemia increased the overflow of norepinephrine in a Ca 2+ ‐independent manner, presumably via the reversed operation of a Na + ‐dependent plasma membrane norepinephrine transporter, and the non‐exocytic release of norepinephrine was blocked by Na + channel antagonists ( Uchihashi et al ., 1998 ). Therefore, the blockade of Na + channels by NS‐7 may have neuroprotective effects that can be mediated via attenuation of exocytic and non‐exocytic secretion of catecholamines.…”

Section: Discussionmentioning

confidence: 99%

Short‐ and long‐term differential effects of neuroprotective drug NS‐7 on voltage‐dependent sodium channels in adrenal chromaffin cells

Yokoo

Shiraishi

Kobayashi

et al. 2000

British J Pharmacology

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1 In cultured bovine adrenal chroman cells, NS-7 [4-(4-¯uorophenyl)-2-methyl-6-(5-piperidinopentyloxy) pyrimidine hydrochloride], a newly-synthesized neuroprotective drug, inhibited veratridine-induced 22 Na + in¯ux via voltage-dependent Na + channels (IC 50 =11.4 mM). The inhibition by NS-7 occurred in the presence of ouabain, an inhibitor of Na + ,K + ATPase, but disappeared at higher concentration of veratridine, and upon the washout of NS-7. 2 NS-7 attenuated veratridine-induced 45 Ca2+ in¯ux via voltage-dependent Ca 2+ channels (IC 50 =20.0 mM) and catecholamine secretion (IC 50 =25.8 mM). 3 Chronic (512 h) treatment of cells with NS-7 increased cell surface [ 3 H]-STX binding by 86% (EC 50 =10.5 mM; t 1/2 =27 h), but did not alter the K D value; it was prevented by cycloheximide, an inhibitor of protein synthesis, or brefeldin A, an inhibitor of vesicular transport from the trans-Golgi network, but was not associated with increased levels of Na + channel a-and b 1 -subunit mRNAs. 4 In cells subjected to chronic NS-7 treatment, 22 Na + in¯ux caused by veratridine (site 2 toxin), ascorpion venom (site 3 toxin) or b-scorpion venom (site 4 toxin) was suppressed even after the extensive washout of NS-7, and veratridine-induced 22 Na + in¯ux remained depressed even at higher concentration of veratridine; however, either a-or b-scorpion venom, or Ptychodiscus brevis toxin-3 (site 5 toxin) enhanced veratridine-induced 22 Na + in¯ux as in nontreated cells. 5 These results suggest that in the acute treatment, NS-7 binds to the site 2 and reversibly inhibits Na + channels, thereby reducing Ca 2+ channel gating and catecholamine secretion. Chronic treatment with NS-7 up-regulates cell surface Na + channels via translational and externalization events, but persistently inhibits Na + channel gating without impairing the cooperative interaction between the functional domains of Na + channels.

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Section: Discussionmentioning

confidence: 99%

Short‐ and long‐term differential effects of neuroprotective drug NS‐7 on voltage‐dependent sodium channels in adrenal chromaffin cells

Yokoo

Shiraishi

Kobayashi

et al. 2000

British J Pharmacology

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“…In most studies, hippocampus, corticostriatum [28,124] spinal cord [112,164] or other brain tissue is chopped or vibratomed into ~400 m thick slices, which are then transferred into either a Haas-type interface recording chamber or a submerged chamber. In the hippocampus, electrophysiology is typically done using a bipolar stimulating electrode on the surface of the Schaffer collaterals, mossy fibers or perforant path, and recording from area CA1, CA3 or dentate gyrus, respectively, is performed.…”

Section: Anoxia/oxygen-glucose Deprivation (Ogd)mentioning

confidence: 99%

Brain Slices as Models for Neurodegenerative Disease and Screening Platforms to Identify Novel Therapeutics

Cho

Wood²,

Bowlby³

2007

218

208

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Recent improvements in brain slice technology have made this biological preparation increasingly useful for examining pathophysiology of brain diseases in a tissue context. Brain slices maintain many aspects of in vivo biology, including functional local synaptic circuitry with preserved brain architecture, while allowing good experimental access and precise control of the extracellular environment, making them ideal platforms for dissection of molecular pathways underlying neuronal dysfunction. Importantly, these ex vivo systems permit direct treatment with pharmacological agents modulating these responses and thus provide surrogate therapeutic screening systems without recourse to whole animal studies. Virus or particle mediated transgenic expression can also be accomplished relatively easily to study the function of novel genes in a normal or injured brain tissue context.In this review we will discuss acute brain injury models in organotypic hippocampal and co-culture systems and the effects of pharmacological modulation on neurodegeneration. The review will also cover the evidence of developmental plasticity in these ex vivo models, demonstrating emergence of injury-stimulated neuronal progenitor cells, and neurite sprouting and axonal regeneration following pathway lesioning. Neuro-and axo-genesis are emerging as significant factors contributing to brain repair following many acute and chronic neurodegenerative disorders. Therefore brain slice models may provide a critical contextual experimental system to explore regenerative mechanisms in vitro.

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“…While it is known that acetylcholine and adrenergic agonists such as noradrenalin are released into the extracellular space of the CNS during ischemia (e.g., Richards et al, 1993;Yamamuro et al, 1996;Uchihashi et al, 1998), recordings of resting and ischemic levels in brain white matter are lacking. The partial conduction block produced by adrenoreceptor antagonists in the current study indicates tonic receptor activation in white matter, and is consistent with the presence of an endogenous release mechanism potentially capable of elevating extracellular noradrenalin to toxic levels during ischemia.…”

Section: Discussionmentioning

confidence: 99%

Conduction block and glial injury induced in developing central white matter by glycine, GABA, noradrenalin, or nicotine, studied in isolated neonatal rat optic nerve

Constantinou

Fern

2009

Glia

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Na+ channel block prevents the ischemia-induced release of norepinephrine from spinal cord slices

Cited by 25 publications

References 41 publications

Short‐ and long‐term differential effects of neuroprotective drug NS‐7 on voltage‐dependent sodium channels in adrenal chromaffin cells

Short‐ and long‐term differential effects of neuroprotective drug NS‐7 on voltage‐dependent sodium channels in adrenal chromaffin cells

Brain Slices as Models for Neurodegenerative Disease and Screening Platforms to Identify Novel Therapeutics

Conduction block and glial injury induced in developing central white matter by glycine, GABA, noradrenalin, or nicotine, studied in isolated neonatal rat optic nerve

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