ライフサイエンスコーパス: sodium current

1 V1.2 mutation displaying enhanced persistent sodium current.

2 creased the transient outward K+ current and sodium current.

3 tment with ranolazine, a blocker of the late sodium current.

4 cardiomyopathy phenotype by reducing cardiac sodium current.

5 enlarged window current, and huge sustained sodium current.

6 FA modulation of TTX-sensitive voltage-gated sodium current.

7 y sodium cyanide to activate this persistent sodium current.

8 NTA1 in cardiac myocytes also increased late sodium current.

9 tributed to preferential suppression of late sodium current.

10 , which also markedly reduced the persistent sodium current.

11 ls, and neither mutation affected persistent sodium current.

12 t contribution of subthreshold TTX-sensitive sodium current.

13 strating a gain-of-function increase in late sodium current.

14 ession of the mutation alone did not produce sodium current.

15 of tetrodotoxin that produced half-block of sodium current.

16 ersely affecting the transient voltage-gated sodium current.

17 ng the amplitude of voltage-gated persistent sodium current.

18 es and prolonged inactivation of the cardiac sodium current.

19 the effect of BjIP on calcium transients and sodium current.

20 ovary cells transfected with SCN5A, encoding sodium current.

21 tion of its recovery or increased persistent sodium current.

22 in excitability resulted from inhibition of sodium currents.

23 selective Nav1.7 channel blocker)-sensitive sodium currents.

24 Cells with AHP expressed greater density of sodium currents.

25 nactivation of Nav1.7 and enhanced resurgent sodium currents.

26 of inactivation and inhibition of persistent sodium currents.

27 s caused use- and voltage-dependent block of sodium currents.

28 and Fyn enhancement of fast inactivation of sodium currents.

29 tion so that depolarizing steps evoke larger sodium currents.

30 in the pipette solution to induce resurgent sodium currents.

31 tude of tetrodotoxin-sensitive and resistant sodium currents.

32 beta-III spectrin complexes fail to enhance sodium currents.

33 ring action potentials and also "persistent" sodium current, a noninactivating TTX-sensitive current

34 d with a reduction in tetrodotoxin-sensitive sodium current, a requirement for much larger depolarizi

35 ngly, drugs known to suppress the persistent sodium current abolished approximately 10 Hz oscillation

36 Riluzole, a blocker of the persistent sodium current, abolished the effect of PGE2 on sigh act

37 that this model can adequately describe the sodium current activation time course in all mammalian c

38 s model captures all major properties of the sodium current activation.

39 tion increases channel availability and late sodium current activity, leading to enhanced cardiac exc

40 ombin amplifies the persistent voltage-gated sodium current affecting resting membrane potential and

41 ity-dependent potentiation of the persistent sodium current altering intrinsic firing properties of d

42 The reduction of sodium current amplitude by estradiol suggests a negativ

43 PHN-associated VZV significantly increased sodium current amplitude in the cell line when compared

44 t studies show that voltage-gated persistent sodium current amplitude is regulated by alternative spl

45 Estradiol decreased the persistent sodium current amplitude, and induced a significant nega

46 radiol significantly decreased the transient sodium current amplitude, but prolonged the sodium curre

47 ed sodium channel protein abundance and peak sodium current amplitudes (H/H, 41.0+/-2.9 pA/pF at -30

48 ting of sodium channels to produce resurgent sodium current, an unusual form of gating in which sodiu

49 -L precipitate a marked decrease in the peak sodium current and a potentially lethal BrS-like proarrh

50 to this property: a persistent TTX-sensitive sodium current and a ruthenium red-sensitive, TRP-like c

51 Both TipE and TEH1 enhanced the amplitude of sodium current and accelerated current decay of all thre

52 This regulation led to a decreased sodium current and action potential upstroke velocity an

53 this variant with mexiletine restored their sodium current and administration of mexiletine to 1 car

54 substantial augmentation of persistent late sodium current and an increase in ramp current.

55 e findings correlated with larger persistent sodium current and depolarized inactivation in neurons f

56 this disease is caused by selective loss of sodium current and excitability of GABAergic inhibitory

57 The mutation results in increased persistent sodium current and hyperactivity of transfected neurons.

58 arkedly augments an inward voltage-sensitive sodium current and inhibits the outward nonselective cur

59 rations of A-803467 selectively block "late" sodium current and shorten action potentials in mouse an

60 plex attached to SCN5A as a key regulator of sodium current and suggest that SNTA1 be considered a ra

61 of at least four voltage-gated currents: the sodium current and the M-type, delayed rectifier, and ca

62 Mexiletine is used to block late sodium current and to shorten QT interval in LQT3 patien

63 to peak, persistent, and resurgent forms of sodium current and to sustained action potential firing.

64 bility is mediated in part by an increase in sodium currents and a reduction in the fast-inactivating

65 on with loss of planarity, reduced resurgent sodium currents and abnormal glutamatergic neurotransmis

66 Similarly, the sodium currents and action potential firing are also imp

67 ns in NaV1.1 channels have severely impaired sodium currents and action potential firing in hippocamp

68 Dravet inhibitory neurons showed deficits in sodium currents and action potential firing, which were

69 halenyl)-2,4-hexadienamide (BTG 502) reduces sodium currents and antagonizes the action of BTX on coc

70 cells by the opponency between depolarizing sodium currents and hyperpolarizing inhibitory currents.

71 s using a mouse model of DS revealed reduced sodium currents and impaired excitability in GABAergic i

72 FGF13 increased Nav1.7 sodium currents and maintained the membrane localization

73 The Possum mutation enhanced Na(v)1.8 sodium currents and neuronal excitability and heightened

74 trodotoxin (TTX)-resistant, SCN10A-dependent sodium currents and response to nociceptive stimuli such

75 egrees C, the mutant channel did not produce sodium current, and function was not restored by coexpre

76 tylcholine activated potassium current, peak sodium current, and L-type calcium current, and exhibits

77 e clusters are major contributors to cardiac sodium current, and that loss of NaV1.5 expression reduc

78 PKP2 expression alters the properties of the sodium current, and the velocity of action potential pro

79 t, without change to transient voltage-gated sodium current, and to rescue of seizure in this model i

80 rents, such as the M-current, and persistent sodium currents are critically involved in generating ap

81 Subthreshold sodium currents are important in sculpting neuronal disc

82 ata supporting the hypothesis that the TTX-R sodium currents are similarly distributed between nodose

83 om an adaptation current and the receptor or sodium current as main sources for the colored and white

84 tivated a substantial component of transient sodium current as well as persistent current.

85 servations are similar to the increased late sodium current associated with LQT3-associated SCN5A mut

86 ctivation of transient as well as persistent sodium current at subthreshold voltages produces amplifi

87 arameters between V232I+L1308F and wild-type sodium currents at baseline, use-dependent inhibition of

88 activation rate to severely suppress cardiac sodium currents at elevated temperatures.

89 saicin induces in small DRG neurons a robust sodium current block within 30 s.

90 e same cell line all four WNKs also increase sodium current blocked by the ENaC inhibitor amiloride.

91 Consistent with increased sodium currents, both types of patient-derived neurons s

92 lso activated a large component of transient sodium current, but IPSP-like waveforms engaged primaril

93 Unexpectedly, it also reduced the peak sodium current by 80%.

94 esulted in a decrease of amiloride-sensitive sodium current by approximately 60% and ciliary length b

95 ding of Fyn kinase and mediate inhibition of sodium currents by enhancing fast inactivation.

96 sion of Fyn with Na(V)1.2 channels decreases sodium currents by increasing the rate of inactivation a

97 e-cell patch-clamp method was used to record sodium currents by subtraction in response to applicatio

98 determined that the increase in a persistent sodium current causes heterogeneously prolonged action p

99 3 results in a 2- to 3-fold increase in late sodium current compared with wild-type caveolin-3.

100 n heterologous cells increased peak and late sodium current compared with WT-SNTA1, and the increase

101 onally, transient, resurgent, and persistent sodium current components showed voltage- and time-depen

102 a2+ influx, as well as reduced voltage-gated sodium currents, consistent with compromised neurite int

103 suggest that, in some CNS neurons, resurgent sodium currents contribute to production of high-frequen

104 Resurgent sodium currents contribute to the regeneration of action

105 ate a natural temperature-dependent shift in sodium current deactivation (exacerbated by mutation) ma

106 nic Kidney-293 cells, showing a reduction in sodium current densities similar to typical BrS mutation

107 underlying mechanism by which MOG1 increased sodium current densities.

108 f MOG1 with Nav1.5 in HEK293 cells increased sodium current densities.

109 s increase was accompanied by an increase in sodium current density and a leftward shift in the sodiu

110 Sodium current density and intrinsic neuronal excitabili

111 ) mice exhibited normalized pyramidal neuron sodium current density and reduced hippocampal NaV1.6 pr

112 Scn2b null atria had normal levels of sodium current density compared with wild type.

113 drome, we found no measurable differences in sodium current density in acutely dissociated CA3 hippoc

114 Sodium current density was half that of wild-type muscle

115 The sodium current density was, however, substantially reduc

116 d neuronal hyperexcitability, suppressed the sodium current density, and right-shifted the V1/2 of th

117 t excessive cleavage of Navbeta2 and reduced sodium current density, but the phenotype associated wit

118 type TRPV1, despite similar or even reduced sodium current density.

119 and was associated with significantly lower sodium current density.

120 ng behaviour was both voltage and persistent sodium current dependent and could be stimulated by sodi

121 nts, albeit all neurons presented persistent sodium current-dependent intrinsic pacemaker properties

122 t widths slows conduction because of reduced sodium current driving force, termed "self-attenuation."

123 me type III (LQT3) is an excessive inflow of sodium current during phase 3 of the action potential ca

124 We quantified these two components of sodium current during the pacemaking trajectory using ac

125 Sodium currents elicited from a holding potential of -60

126 C, but lamotrigine also increased persistent sodium current evoked by this mutation.

127 chanisms underlying the increased persistent sodium current exhibited by the GEFS+ mutant R1648H.

128 sult from increased voltage-gated persistent sodium current expression.

129 gical mechanism whereby calcium ions promote sodium current facilitation due to Ca(2+) memory at high

130 gy, as prolonged pharmacological blockade of sodium current failed to phenocopy channel knockdown.

131 of action potential, we show that resurgent sodium current flows at the peak of afterhyperpolarizati

132 eak of afterhyperpolarization and persistent sodium current flows in the middle of the interspike int

133 need for a high-fidelity technique to record sodium currents from intact mouse muscle fibres.

134 ned the effects of cannabidiol on endogenous sodium currents from striatal neurons, and similarly we

135 ated the ability of cannabinoids to modulate sodium currents from wild-type and epilepsy-associated m

136 erformed high temporal resolution studies of sodium currents gating in three types of central neurons

137 Whereas TTX-R sodium currents have been documented in lung vagal senso

138 ulted in a complete disruption of the normal sodium current heterogeneity that exists between atrial,

139 of the tetrodotoxin-resistant, voltage-gated sodium current I(Na) in alphaMyHC-FKBP12 ventricular car

140 The persistent sodium current (I(Na(P))) has been implicated in the reg

141 In addition, we characterized TTX-sensitive sodium current (I(Na)) and 4AP-sensitive and TEA-resista

142 bserved that loss of Pum2 leads to increased sodium current (I(Na)) and action potential firing, mimi

143 al repressor Pumilio (Pum) as a regulator of sodium current (I(Na)) and excitability in Drosophila mo

144 (0.5-2 mumol/L) had no effect on either mean sodium current (I(Na)) density or I(Na) gating kinetics

145 sma membrane (PM) expression of Na(v)1.5 and sodium current (I(Na)) density, thus we hypothesize that

146 tress has been shown to increase late inward sodium current (I(Na)), reducing the net cytosolic Ca(2+

147 the cell resting membrane potential, and the sodium current (I(Na)), which provides a rapid depolariz

148 variable, whereas blockade of the persistent sodium current (I(NaP)) abolished them.

149 s also demonstrate an increase in persistent sodium current (I(NaP)) and a hyperpolarizing shift in t

150 dominated by inward TTX-sensitive persistent sodium current (I(NaP)) that activated near -75 mV and i

151 ting activity that depends upon a persistent sodium current (I(NaP)).

152 We compared sodium currents (I(Na)) in small DRG neurons from beta2+

153 d potassium currents (I(KNa)) and persistent sodium currents (I(NaP)), the components of which are wi

154 Resurgent sodium currents (I(NaR)) are atypical currents believed

155 , a noninactivating, persistent component of sodium current, I(NaP), has been implicated in integrati

156 yperpolarized potentials, and the persistent sodium current, I(NaP), which prolonged and amplified IP

157 that CaMKII-mediated modulation of neuronal sodium current impacts neuronal excitability in Scn2a(Q5

158 isplaying lower amplitudes of a "persistent" sodium current important for such pacemaking.

159 We examined gating of subthreshold sodium current in dissociated cerebellar Purkinje neuron

160 c insights into the central role of the late sodium current in HCM, and introduce the scientific rati

161 Scn10a expression contributes to late sodium current in heart and represents a new target for

162 Electrophysiological analysis of sodium current in HEK293 cells stably expressing hNa(v)1

163 ing abnormality is an increase in persistent sodium current in hippocampal neurons.

164 estradiol modulated a tetrodotoxin-sensitive sodium current in isolated GnRH neurons from both young

165 n important role for these components of the sodium current in Mes V neuron electrogenesis.

166 only approximately 20% of the TTX-resistant, sodium current in mouse dorsal root ganglion neurons.

167 ls was specific because POSH did not inhibit sodium current in oocytes injected with ENaC-alpha, beta

168 Nonlinear loss of sodium current in Purkinje neurons from heterozygous and

169 channels a capacity to serve as a pacemaking sodium current in the primitive heart and brain in lieu

170 ing site of Na(v)1.6 prevented generation of sodium current in transfected cells.

171 n potential firing by blocking voltage-gated sodium currents in a subset of somatosensory neurons, wh

172 ntially increased the amplitude of resurgent sodium currents in an optimized adult rat-derived dorsal

173 mpal mossy fibers of adult mice, we recorded sodium currents in axonal and somatic membrane patches.

174 DS patient-derived neurons show increased sodium currents in both bipolar- and pyramidal-shaped ne

175 ontrast, Ae1a failed to significantly affect sodium currents in dorsal unpaired median neurons from t

176 l administered to the female mouse modulates sodium currents in fluorescently-labeled GnRH neurons.

177 locked, albeit with varying potencies, TTX-r sodium currents in frog dorsal-root-ganglion (DRG) neuro

178 Our results indicate that reduced sodium currents in GABAergic inhibitory interneurons in

179 Here we show that FFA inhibits voltage-gated sodium currents in hippocampal pyramidal neurons; this e

180 , flagellin/QX-314 co-application suppressed sodium currents in large-diameter human DRG neurons.

181 and modulate the expression of TTX-resistant sodium currents in medium-sized muscle nociceptors.

182 biophysical properties of VGSCs, we isolated sodium currents in MSO principal neurons in gerbil brain

183 eceptors, was found to inhibit voltage-gated sodium currents in N1E-115 neuroblastoma cells.

184 onsequence, reduce voltage-gated calcium and sodium currents in primary sensory neurons.

185 f whole-cell peak, persistent, and resurgent sodium currents in Purkinje neurons were reduced by 58-6

186 significantly less potent in blocking TTX-r sodium currents in rat and mouse DRG neurons.

187 atives, such as 7 and 27, also blocked TTx-r sodium currents in rat dorsal root ganglia (DRG) neurons

188 his study was to examine the contribution of sodium currents in the negative feedback action of estra

189 Hodgkin and Huxley established that sodium currents in the squid giant axons activate after

190 the early (peak) and late components of the sodium current (INa and INaL), but ranolazine preferenti

191 ties of one pacemaker rely on the persistent sodium current (INa(p)) and are insensitive to blockade

192 H 7.4, VCL-M94I caused 30% decrease in peak sodium current (INa) amplitude compared to WT; under aci

193 1768D/+) mice showed increases in persistent sodium current (INa) density in CA1 pyramidal but not bi

194 Whole-cell patch-clamp was used to measure sodium current (INa) density in isolated cardiomyocytes.

195 h was paralleled by a higher Ito and a lower sodium current (INa) density in subepicardium versus sub

196 regulatory proteins that reduce or eliminate sodium current (INa) have been linked to BrS.

197 cardiac sodium channel, NaV1.5, carries the sodium current (INa) that provides a rapid depolarizing

198 mice displayed reduced NaV1.5 expression and sodium current (INa), specifically at the lateral myocyt

199 rons to hypoxia-an increase in voltage-gated sodium current (INa)-has been unknown.

200 oke velocity because of a 2-fold increase in sodium current (INa).

201 iting potassium currents and increasing late sodium current (INa-L) in cardiomyocytes.

202 polarization additionally by increasing late sodium current (INa-L) via inhibition of phosphoinositid

203 To determine whether increased sodium current(INa) would promote EADs, we employed aden

204 odels incorporate a formulation of the rapid sodium current, INa, based on 30 year old data from chic

205 sodium current amplitude, but prolonged the sodium current inactivation time constant.

206 o inactivate, contributing to increased late sodium current (INaL), which is directly responsible for

207 tiple ion currents, including the persistent sodium current INaP.

208 cal cable theory predictions, the persistent sodium current (INaP), a non-inactivating mode of the vo

209 d that riluzole, a blocker of the persistent sodium current (INap), abolished the modulatory effect o

210 ability through regulation of the persistent sodium current (INaP).

211 nd inhibition of transient voltage-sensitive sodium current (INaT) as a measure of D1 receptor functi

212 monstrated a dramatic increase in persistent sodium current, incomplete channel inactivation, and a d

213 PHN-associated VZV sodium current increases were therefore mediated in part

214 These sodium current increases were unaffected by acyclovir pr

215 ationale and execution of the Impact of Late Sodium Current Inhibition on Exercise Capacity in Subjec

216 ty in L-cells was due to large voltage gated sodium currents, inhibition of which by tetrodotoxin red

217 Resurgent sodium current is an atypical near threshold current pre

218 ly, pharmacological induction of a transient sodium current is capable of restoring regeneration even

219 Exaggerated late sodium current is known to mediate arrhythmogenic early

220 found that non-voltage-dependent background sodium current is much smaller in SNc neurons than VTA n

221 A subthreshold sodium current is necessary for a continuous frequency d

222 We found that TTX-sensitive sodium current is the main inward current flowing during

223 current, in combination with the persistent sodium current, is essential to respiratory rhythm in vi

224 Diminution of sodium currents, largely NaV1.7, was recapitulated in se

225 a inhibition of the late phase of the inward sodium current (late I(Na)) during cardiac repolarizatio

226 Late sodium current (late INa) is enhanced during ischemia by

227 a marked increase in both the peak and late sodium currents leading to prolongation of the action po

228 isolated CAR(+)/(-) myocytes showed reduced sodium current magnitude specifically at the intercalate

229 as AP maximum upstroke velocity, whole-cell sodium current magnitude/properties, and mRNA levels of

230 ctive" mutations affecting calcium-dependent sodium currents mapped to the N-domain, while "over-reac

231 , and that enhanced resurgent and persistent sodium currents may provide a general mechanistic basis

232 + neurons, brought about in part by enhanced sodium currents, may contribute to the spontaneous itch-

233 transcripts, Na(V)1.5 protein abundance, and sodium current measured in isolated ventricular myocytes

234 However, sodium currents measured in the Orai3-expressing HEK293

235 a(+)](o) modulate neuronal excitability by a sodium current mechanism and that excessively altered ne

236 In contrast, Dc1a has little effect on sodium currents mediated by PaNav1 channels from the Ame

237 mutation has been shown to disrupt both the sodium-current-modulatory and cell-adhesive functions of

238 dings revealed that two currents, persistent sodium current (NaP) and K(+)-dominated leak current (Le

239 marily motoneurons, inhibition of persistent sodium current (NaP) by the drug riluzole at low concent

240 leptic drugs target voltage-gated persistent sodium current, none exclusively repress this current wi

241 -E did not prevent heptanol-induced block of sodium currents, nor did it alter voltage dependence or

242 oncentrations, KIIIA incompletely blocks the sodium current of Na(V)1.2, leaving a 5% residual curren

243 effects of the novel analogs were tested on sodium currents of native myofibers.

244 substantial contribution from the transient sodium current or bulk [Na(+)](i).

245 ent had no effect on either pyramidal neuron sodium current or hippocampal NaV1.6 levels.

246 nabidiol can preferentially target resurgent sodium currents over peak transient currents generated b

247 natal mouse myocytes markedly attenuated the sodium current (P<0.01).

248 s HEK cells produced a significantly reduced sodium current (P<0.01).

249 n-inactivating mode of the voltage-dependent sodium current, paradoxically increases Rin and taum whe

250 und that the activity of a persistent inward sodium current (persistent I(Na)) is highly effective at

251 These results suggest that the persistent sodium current plays a major role in determining firing

252 X-314, leading to TLR5-dependent blockade of sodium currents, predominantly in A-fiber neurons of mou

253 butes to QT prolongation by altering cardiac sodium current properties (INa).

254 exhibited significantly increased persistent sodium currents (range, 0.5% to 1.7% of peak current) ty

255 11F, P1632S and F1808L) exhibited persistent sodium current ranging from approximately 1-3% of peak c

256 ects of GS967 on peak (INaP) and late (INaL) sodium current recorded from cells that heterologously e

257 sm whereby waveform changes from the reduced sodium current (reduced spike height and a hyperpolarizi

258 eads to conduction slowing, especially after sodium current reduction.

259 alcn, a unique channel that generates "leak" sodium currents, regulates excitability and neuromodulat

260 s: the deactivation threshold for persistent sodium currents reversibly shifts to a more negative vol

261 ificant reduction in L-type calcium and peak sodium current, shortening of action potential duration

262 icular excitability via 20% reduction of the sodium current should increase vulnerability to life-thr

263 mp experiments showed an increased sustained sodium current, suggesting a mechanistic overlap between

264 e that lack Na(v)1.6, reduces tetrodotoxin-S sodium currents, suggesting isoform-specific modulation

265 model, which has no axon or spike-generating sodium currents, suggests that MSO spikes do not contrib

266 nd discusses BACE physiological functions in sodium current, synaptic transmission, myelination, and

267 Furthermore, in addition to the transient sodium current that flows during the upstroke of action

268 The sodium current that initiates the nerve action potential

269 otype by reducing the driving force and late sodium current that produces early afterdepolarizations

270 ead to increased resurgent currents, unusual sodium currents that have not previously been implicated

271 Voltage-gated sodium channels (Nav) produce sodium currents that underlie the initiation and propaga

272 The sensitivity of the sodium current to shaking was dependent on intact cilia.

273 of BDNF to enhance a tetrodotoxin-resistant sodium current (TTX-R I(Na)) and to suppress a delayed r

274 Although L1825P generates late sodium current typical of SCN5A-linked long-QT syndrome

275 stradiol did not significantly attenuate the sodium current underlying the action potential in cells

276 The amplitude of the sodium current underlying the action potential was signi

277 Persistent tetrodotoxin-resistant (TTX-r) sodium currents up-regulated by intracellular GTP have b

278 Importantly, this reduction in sodium current was also seen when the atypical mutations

279 Previously unobtainable robust sodium current was demonstrated through 38 passages, sui

280 Persistent sodium current was found to account for most of the PIC

281 Sodium current was lower when NaV1.5 was coexpressed wit

282 However, for narrow clefts, late sodium current was reduced via self-attenuation, a prote

283 TTX-sensitive sodium current was substantial throughout the entire int

284 The hypothesis that a persistent sodium current was the predominant determinant of cell f

285 Sodium currents were acquired by whole cell recording on

286 Sodium currents were examined using standard whole-cell

287 Whole-cell sodium currents were measured in tsA201 cells transientl

288 In contrast, sodium currents were not found in sustained ON bipolar c

289 Only L263V and Q1489K generated quantifiable sodium currents when coexpressed in tsA201 cells with th

290 pical mutations could lead to a reduction in sodium currents when coexpressed with WT to mimic the he

291 lator, in which gasping relies on persistent sodium current, whereas eupnea does not depend on this c

292 CN5A, and was associated with increased late sodium current, which is the characteristic biophysical

293 d slows down the inactivation process of the sodium current, while shifting the inactivation curve ~1

294 utant channel revealed significantly delayed sodium current with a dominant negative effect.

295 -like waveforms engaged primarily persistent sodium current with only a small additional transient co

296 mutations in SCN5A result in a reduction of sodium current with some mutations even exhibiting a dom

297 t channel generated voltage-dependent inward sodium currents with an average peak current density com

298 isoforms produce a multiplicity of distinct sodium currents with different time-dependent characteri

299 -cell configuration, carbamazepine inhibited sodium current within seconds when applied externally, b

300 ficant reduction in voltage-gated persistent sodium current, without change to transient voltage-gate