ライフサイエンスコーパス: HERG

1 KCNH2 that encodes for p.T152HfsX180 Kv11.1 (hERG).

2 than a 3000-fold selectivity for PDE1B over hERG.

3 70-independent quality control E3 ligase for hERG.

4 at position Gly-603 in the S5-pore linker of hERG.

5 izing cell population, and the expression of hERG.

6 eptide corresponding to the E-pore region of HERG.

7 around 13% at 10 muM, comparable to that of hERG.

8 interaction between the sigma-1 receptor and hERG.

9 be copurified with an Ab against the nascent hERG 1a N terminus.

10 how that shRNA specifically targeting either hERG 1a or 1b transcripts reduced levels of both transcr

11 Despite these findings, adoption of hERG 1a/1b heteromeric channels as a model for cardiac I

12 s encoding human ether-a-go-go-related gene (hERG) 1a and 1b subunits, which assemble to produce ion

13 expressed human ether a-go-go-related gene (hERG) 1a/1b channels, which more closely resemble rapidl

14 These findings establish that hERG 1b is critical for normal repolarization and that l

15 The human ether-a-go-go-related gene encodes hERG, a cardiac voltage-gated K(+) channel that is abnor

16 hERG) or 1-136 of the N terminus (DeltaN 136 hERG) abolished acute PMA (30 nM, 30 minutes)-mediated I

17 ansitions through early closed states of the hERG activation pathway, and that the weak voltage depen

18 ng and selecting BKIs with minimum levels of hERG activity and frequencies of other safety liabilitie

19 Selected compounds were tested for in vitro hERG activity and in vivo efficacy in the P. berghei mou

20 A balance of low Pgp efflux and hERG activity was achieved by lowering the polar surface

21 ibition in vitro, anti-human Src inhibition, hERG activity, in vivo pharmacokinetic data, and efficac

22 anti-human ether-a-go-go potassium channel (hERG) activity of the first-generation anti-Cryptosporid

23 Reduction of hERG affinity led to greater than a 3000-fold selectivit

24 lternative, with good blood stability and no hERG affinity, providing new opportunities for the serie

25 erved, while some of the compounds exhibited hERG affinity.

26 which became larger than untreated control I(hERG) after PMA removal for 4 hours.

27 hERG alteration by mutation or pharmacological inhibitio

28 eracts through the transmembrane region with hERG and decreases hERG functional expression.

29 (30 nM, 16 hours) increased both Delta2-354 hERG and DeltaN136 hERG expression levels and currents.

30 hERG and hNav1.5 block.

31 eta-arrestin signaling-mediated increases in hERG and IKr were also observed in hERG-HEK cells as wel

32 chimeric channel between protease-sensitive hERG and insensitive human ether-a-go-go (hEAG), as well

33 D2 receptors and negligible interactions at hERG and M1 receptors.

34 n LQT2 patients with functional mutations in hERG and matched healthy participants, testing the hypot

35 It is devoid of hERG and phospholipidosis issues.

36 nM, 30 minutes) reduced both hERG current (I(hERG)) and I(Kr) Chronic activation of PKC by PMA (30 nM

37 oncentrations, verapamil blocked hCav1.2 and hERG, as did vanoxerine and bepridil both of which also

38 enesis, we identified that calpain-1 cleaves hERG at position Gly-603 in the S5-pore linker of hERG.

39 ed into the extracellular milieu and cleaved hERG at the S5-pore linker.

40 strated that fentanyl blocks hERG current (I(hERG)) at concentrations that overlap with the upper ran

41 ly we propose that trafficking inhibition of hERG be added to CiPA.

42 Sig1R promoted the formation of hERG/beta1-integrin signaling complexes upon extracellul

43 on of polar groups was effective in reducing hERG binding affinity, this came at the expense of highe

44 ubility and microsomal stability and reduced hERG binding.

45 ytes by combining effects of a hormone and a hERG blocker, dofetilide, or hERG mutations.

46 Kv11.1 (hERG) blockers with comparable potencies but different b

47 n-platform variance predominated for 4 of 12 hERG blocking drugs and 4 of 6 hNav1.5 blocking drugs.

48 ared vanoxerine with dofetilide, a selective hERG-blocking torsadogen used for intractable AF, verapa

49 Dysfunction of hERG causes long QT syndrome and sudden death, which occ

50 ocyte model modified to include dynamic drug-hERG channel (human Ether-a-go-go-Related Gene) interact

51 The activation kinetics of hERG channel activation are much faster, but inactivatio

52 macological scenarios associated with slower hERG channel activation because of the increased chances

53 hypothermia or the other scenarios that slow hERG channel activation.

54 of a model activator (NS1643) action on the hERG channel and its L529I mutant.

55 tested on IKr using HEK293 cells expressing HERG channel and native cardiac myocytes.

56 isk are more likely to be trapped within the hERG channel and show stronger reverse use dependency of

57 ompounds also have high selectivity over the hERG channel and were characterized with respect to thei

58 o the presence of hERG1b in the human heart, hERG channel block by fentanyl can be exacerbated by cer

59 chronic incubation (for 2-3 weeks) with the hERG channel blocker dofetilide (100 nM), whereas more a

60 used minimal acute cardiotoxicity based on a hERG channel blocking assay and an unappreciable chronic

61 In vitro hERG channel current recordings are an important step in

62 g, as N-Cap deletion drastically accelerates hERG channel deactivation.

63 Drug-induced disruption of hERG channel function is a main cause of acquired long Q

64 and establish that allosteric modulation of hERG channel function through ligand binding to the PAS

65 Changes in hERG channel function underlie long QT syndrome (LQTS) a

66 positive sera showed the predominance of the HERG channel in controlling action potential duration an

67 trafficking to the membrane, unlike for the hERG channel in which N-Cap and PAS domain truncations m

68 We found that AMD enhances hERG channel inactivation but slows activation as well a

69 on in immunized guinea-pigs by targeting the HERG channel independently from fibrosis.

70 ion connecting the S5 and S6 segments of the HERG channel induces high titres of antibodies that inhi

71 Modeling dynamic drug-hERG channel interactions and multi-ion channel pharmaco

72 homology between anti-52-kDa Ro antigen and HERG channel is present.

73 use high-throughput systems to capture full hERG channel kinetics quantitatively and rapidly.

74 eases inhibit IKr by cross-reacting with the HERG channel likely at the pore region where homology be

75 repolarization, suggesting that the rates of hERG channel opening and, critically, that of deactivati

76 de blockade can concur simultaneously in the hERG channel pore.

77 s, its binding to a H3 receptor as well as a hERG channel prevented it from further development.

78 otential duration by directly binding to the HERG channel protein.

79 identify residues in the outer turret of the hERG channel that act as a proton sensor to regulate ope

80 Thus, it is important to understand hERG channel trafficking and its regulation.

81 While lumacaftor is an effective hERG channel trafficking chaperone and may be therapeuti

82 Inhibition of the HERG channel was assessed by electrophysiology and by co

83 We found that AMD binds to the resting hERG channel with an apparent dissociation constant of ~

84 ivity in the SafetyScreen44 panel (including hERG channel), high solubility, metabolic stability, and

85 e of proarrhythmic drug interaction with the hERG channel, to the fundamental cellular and tissue-lev

86 el of receptors including 5-HT2B subtype and hERG channel, which suggests no major cardiac issues.

87 We conclude that AMD is an effective hERG channel-gating modifier capable of lengthening the

88 no relevant affinity for off-target M1R and hERG channel.

89 vant concentrations, these drugs blocked the hERG channel.

90 IKr using HEK293 cells stably expressing the hERG channel.

91 d electrophysiological interference with the hERG channel.

92 ed these values to model drug effects on the hERG channel.

93 en death, we investigated its effects on the hERG channel.

94 easure the human ether-a-go-go-related gene (hERG) channel block (the primary mechanism by which drug

95 cus on the human Ether-a-go-go-Related Gene (hERG) channel, which is important in drug safety assessm

96 e are associated with alterations in Kv11.1 (hERG) channel-controlled repolarizing IKr currents of ca

97 activity with a peptide corresponding to the hERG-channel pore-forming region.

98 icantly inhibited IKr and cross reacted with hERG-channel proteins.

99 tabilizes these early closed states, leaving hERG channels able to activate at a rate similar to conv

100 analyses, we demonstrated that internalized hERG channels can effectively recycle back to the plasma

101 ing phorbol 12-myristate 13-acetate (PMA) on hERG channels expressed in human embryonic kidney cell l

102 ransfection of native (WT) and p.T152HfsX180 hERG channels generated a current that was indistinguish

103 exerted "chaperone-like" effects over native hERG channels in both CHO cells and mouse atrial-derived

104 We reported previously that hERG channels in the plasma membrane undergo vigorous in

105 Slow deactivation of hERG channels is critical for preventing cardiac arrhyth

106 d its relationship to the slow activation of hERG channels is not understood.

107 eath need further investigation, blockade of hERG channels may contribute to the death of individuals

108 nterference with the function of the cardiac hERG channels represents one of the major sources of dru

109 uggest that Tbx20 controls the expression of hERG channels responsible for the rapid component of the

110 Currents of hERG channels stably expressed in HEK293 cells were reco

111 ctivated voltage sensor limits the return of hERG channels to rest.

112 y analyzed the KCNH2 (encoding for Kv11.1 or hERG channels) and TBX20 (encoding for the transcription

113 In contrast to wild-type hERG channels, chronic activation of PKC by PMA (30 nM,

114 riant, hERG1a, has been widely used to study hERG channels, coexpression with the short variant, hERG

115 function or decrease the expression level of hERG channels, leading to long QT syndrome.

116 tly, we characterized mode-shift behavior in hERG channels, which results from stabilization of activ

117 H potentiated the fentanyl-mediated block of hERG channels, with an IC(50) at pH 8.4 being 7-fold low

118 itions limits the overall activation rate of hERG channels.

119 ut not Rab4, is involved in the recycling of hERG channels.

120 in the homeostasis of plasma membrane-bound hERG channels.

121 s, without interacting with M1 receptors and hERG channels.

122 hniques to characterize the action of AMD on hERG channels.

123 1 human ether-a-go-go related gene (Kv11.1) (hERG) channels, encoded by the KCNH2 gene, is associated

124 Dissociation of hERG complexes containing Hsp70 and the E3 ubiquitin lig

125 PKC by PMA (30 nM, 30 minutes) reduced both hERG current (I(hERG)) and I(Kr) Chronic activation of P

126 We have demonstrated that fentanyl blocks hERG current (I(hERG)) at concentrations that overlap wi

127 epolarization, fentanyl and naloxone blocked hERG current (I(hERG)) with IC(50) values of 0.9 and 74.

128 nts (e.g., 10.4-fold for dofetilide block of hERG current and 4-fold for mexiletine block of hNav1.5

129 It reduces the amplitude of hERG current and speeds up deactivation, which can alter

130 mia, and alkalosis can increase the block of hERG current by fentanyl, potentially increasing the ris

131 A reduction in the hERG current causes long QT syndrome, which predisposes

132 lcium current, as well as replacement of the hERG current model.

133 rotons regulate the amplitude of macroscopic hERG current.

134 x20 enhanced human KCNH2 gene expression and hERG currents (IhERG) and shortened action-potential dur

135 e group of small molecules that can activate hERG currents and thus may act as potent antiarrhythmic

136 rtantly, AMD no longer inhibits but enhances hERG currents at a mild pulse shortly after a prepulse a

137 rential inhibition and enhancement effect on hERG currents at different phases of membrane voltage ch

138 sociation constant of ~1.4 muM, and inhibits hERG currents at mild and strong depolarization pulses b

139 ibed class III antiarrhythmic, could inhibit hERG currents with relatively few tachyarrhythmic advers

140 0/Hsp70 chaperones assist the folding of the hERG cytosolic domains.

141 c stability in human liver microsomes, and a hERG/DAT affinity ratio = 28.

142 p70 nucleotide exchange factor Bag1 promotes hERG degradation by the ubiquitin-proteasome system at t

143 The interaction with Bag1 then shifts hERG degradation to the membrane-anchored E3 ligase TRC8

144 edd4-2, an E3 ubiquitin ligase that mediates hERG degradation.

145 293A cells partially abolished RFFL-mediated hERG degradation.

146 hERG dimers and tetramers became both singly and doubly

147 st to demonstrate that inhibitory Abs to the HERG E-pore region induce QTc prolongation in immunized

148 elevated total and membrane HERG protein and HERG-encoded current density by approximately 30-50%, wh

149 The human ether-a-go-go-related gene (hERG) encodes the channel that conducts the rapidly acti

150 The human ether-a-go-go-related gene (hERG) encodes the pore-forming subunit of the rapidly ac

151 The human ether-a-go-go-related gene (hERG) encodes the pore-forming subunit of the rapidly ac

152 The human ether-a-go-go-related gene (hERG) encodes the pore-forming subunit of the rapidly ac

153 Human ether-a-go-go-related gene (hERG) encodes the pore-forming subunit of the rapidly ac

154 Loss-of-function mutations in hERG (encoding the Kv11.1 voltage-gated potassium channe

155 ic receptor-based DREADD (M3D-arr) in stable hERG-expressing human embryonic kidney (HEK) cells, we d

156 und that M3D-arr activation increased mature hERG expression and current.

157 posure to low K(+) medium but also decreased hERG expression and function in cells under normal cultu

158 , coexpression of RNF207 and HSP70 increased HERG expression compared with HSP70 alone.

159 increased both Delta2-354 hERG and DeltaN136 hERG expression levels and currents.

160 Clarification of protease-mediated damage of hERG extends our understanding of hERG regulation.

161 One potential link between stress and hERG function is protein kinase C (PKC) activation; howe

162 or medical condition-mediated disruption of hERG function is the primary cause of acquired long-QT s

163 transmembrane region with hERG and decreases hERG functional expression.

164 8 also mediates degradation of the misfolded hERG-G601S disease mutant, but pharmacological stabiliza

165 e characterize the temperature dependence of hERG gating by fitting the parameters of a mathematical

166 flicting results regarding PKC regulation of hERG have been reported.

167 reases in hERG and IKr were also observed in hERG-HEK cells as well as in neonatal rat ventricular my

168 properties of mutations within an overlooked hERG helix, finding important contributions to channel f

169 of some ion channels and in particular, the hERG (human Ether-a'-go-go-Related Gene) cardiac potassi

170 The KCNH2-encoded Kv11.1 hERG (human ether-a-go-go related gene) potassium channe

171 We further engineered a hERG (human ether-a-go-go-related gene) channel, which,

172 domain K(+) (K(2P)) channels, voltage-gated hERG (human ether-a-go-go-related gene) channels and cal

173 d the hypothesis that anti-Ro Abs target the HERG (human ether-a-go-go-related gene) K(+) channel, wh

174 The HERG (human Kv11.1a) channel has previously been shown t

175 ult of unintentional blockade of the Kv11.1 (hERG [human ether-a-go-go-related gene]) channel are a m

176 c risk) against four human cardiac currents (hERG [I(Kr)], hCav1.2 [L-Type I(Ca)], peak hNav1.5, [Pea

177 rents representing IKr (CHO cells expressing hERG; IC50=219+/-21 mumol/L) and IKs (CHO cells expressi

178 n blotting analysis, we demonstrate that the hERG/IKr channel was selectively cleaved by the serine p

179 We conclude that PKC regulates hERG in a balanced manner, increasing expression through

180 ect, and small interfering RNA inhibition of hERG in beta and L cells increased insulin and GLP-1 sec

181 +) channel human ether-a-go-go-related gene (hERG) in myeloid leukemia and colorectal cancer cell lin

182 rms of its microsomal stability, and CYP and hERG inhibition, along with an excellent brain penetrati

183 co-2 permeability/efflux, CYP3A4 inhibition, hERG inhibition, and rat microsomal extraction ratio (ER

184 We found that CYP3A4 inhibition, hERG inhibition, Caco-2 permeability, and efflux are unl

185 axin inhibitor lead compound 1, to attenuate hERG inhibition, remove CYP3A4 time-dependent inhibition

186 s which mitigated the residual weak in vitro hERG inhibition.

187 w liabilities associated with metabolism and hERG inhibition.

188 to oral dosing while controlling CYP450 and hERG inhibitory properties.

189 has potent human ether-a-go-go-related gene (hERG) inhibitory activity, associated with long Q-T synd

190 highly specific (zero false positives on 50 hERG-insensitive drugs), low-cost hERG safety assay.

191 nd undesired off-target pharmacology such as hERG interactions.

192 Low K(+)-enhanced hERG internalization is accompanied by an increased rate

193 In the present study, we addressed whether hERG internalization occurs under normal K(+) conditions

194 ophysical Perspective, we look at what makes hERG intriguing and vexingly unique.

195 Attenuation of hERG ion channel activity inherent within the initial ch

196 pound 4c did not exhibit any activity on the hERG ion channel and pan-assay interference compounds li

197 logical function and monolayers' response to hERG ion channel specific blocker was Torsades de Pointe

198 The human ether-a-go-go-related gene1 (hERG) ion channel has been the subject of fascination si

199 off-target human ether-a-go-go-related gene (hERG) ion channel inhibition were dependent on lipophili

200 ich encodes the cardiac human ether-a-go-go (hERG) ion channel, have been associated with sudden card

201 ge movement can only partly account for slow hERG ionic activation, and that the rate of pore closure

202 BK channel is functionally redundant whereas hERG is essential.

203 -1, we identified that the S5-pore linker of hERG is the target domain for proteinase K cleavage.

204 Kv11.1 (hERG) is a voltage-gated potassium channel that shows ve

205 ovement in human ether-a-go-go-related gene (hERG) is slow, as is return of charge upon repolarizatio

206 Although a potent blocker of hERG, it produced no serious adverse events.

207 d C235 Pf clones, low inhibitory activity in hERG K(+) channel blockage testing, negativity in the Am

208 hERG K(+) channel is important for controlling the durat

209 Relaxation of a hERG K(+) channel model during molecular-dynamics simula

210 mpound 32d, elicited only weak inhibition of hERG K(+) channels and hNaV1.5 Na(+) channels, and no ef

211 It is known that amiodarone (AMD) acts on hERG K(+) channels to treat cardiac arrhythmias with rel

212 Eventually, hERG K-channel block was identified as the main limitati

213 nhibit the human ether-a-go-go-related gene (HERG) K(+) channel at the extracellular pore (E-pore) re

214 target the human ether-a-go-go-related gene (HERG) K(+) channel by inhibiting the corresponding curre

215 isoforms KCNE3S and KCNE4S, KCNE3L inhibited hERG; KCNE4L inhibited Kv1.1; neither form regulated the

216 adation of human ether-a-go-go-related gene (hERG, KCNH2) transcripts containing premature terminatio

217 fit using our 15-s protocol best represents hERG kinetics at any given temperature and suggests that

218 ng the parameters of a mathematical model of hERG kinetics to data obtained at five distinct temperat

219 tocol to study the temperature dependence of hERG kinetics using Chinese hamster ovary cells overexpr

220 ent a new 15 second protocol to characterize hERG (Kv11.1) kinetics, suitable for both manual and hig

221 man ether-a-go-go-related potassium channel (hERG, Kv11.1) is a voltage-dependent channel known for i

222 tem at the endoplasmic reticulum to regulate hERG levels and channel activity.

223 rtain of these compounds exhibited potential hERG liabilities.

224 TgCDPK1 inhibitor 32, which does not have a hERG liability and possesses a favorable pharmacokinetic

225 erivative does not display the same level of hERG liability as observed with 1 and represents a promi

226 3)H]astemizole competitive binding assay for hERG liability screening.

227 Mitigation of a potential Ames and hERG liability ultimately led to two promising compounds

228 SPR519 did not show any CYP or hERG liability.

229 sor-pore interface drive the channel into an hERG-like inactivated state, thereby obscuring its openi

230 Damage of hERG mediated by proteases such as calpain may contribut

231 ell-specific variants/parameterizations of a hERG model at 25 degrees C.

232 bly decorated by sigma-1 receptors; however, hERG monomers were only singly decorated.

233 is not due to enhanced protein synthesis, as hERG mRNA expression was not altered by low K(+) exposur

234 interactions of oestrogen with the pore loop hERG mutation (G604S).

235 dogenic effects: oestradiol interaction with hERG mutations in the pore loop containing G604 or with

236 a hormone and a hERG blocker, dofetilide, or hERG mutations.

237 IKur current blocker with selectivity versus hERG, Na and Ca channels, and an acceptable preclinical

238 Mutations in hERG or drugs can impair the function or decrease the ex

239 V)10.1 and human ether-a-go-go-related gene (hERG or K(V)11.1), have revealed an original nondomain-s

240 ological selectivity or safety risks such as hERG or phospholipidosis.

241 ion of amino acid residues 2-354 (Delta2-354 hERG) or 1-136 of the N terminus (DeltaN 136 hERG) aboli

242 large-conductance KCa1.1, Kv1.2/1.3, Kv7.4, hERG, or inwardly rectifying K(+) channels.

243 The human ether-a-go-go-related gene (hERG; or KCNH2) encodes the voltage-gated potassium chan

244 ances exacerbate fentanyl-induced block of I(hERG) Our results show that chronic hypoxia or hypokalem

245 permeability, reduced Caco-2 efflux, reduced hERG PC activity, and increased selectivity profile whil

246 L is an important regulator of voltage-gated hERG potassium channel activity and therefore cardiac re

247 associated long-QT syndrome by targeting the hERG potassium channel and inhibiting the related curren

248 The hERG potassium channel influences ventricular action pot

249 A dataset of 55 hERG potassium channel inhibitors collected from Kramer

250 In addition, affinity toward the hERG potassium channel of compound 30 was significantly

251 4K2009 is also moderately active against the hERG potassium channel.

252 orm of the human ether-a-go-go-related gene (hERG) potassium channel interact.

253 The human human ether-a-go-go-related gene (hERG) potassium channel plays a critical role in the rep

254 ons in the human ether a go-go-related gene (hERG) potassium channel, many of which cause misfolding

255 as desired, the human ether-a-go-go-related (hERG) potassium channel.

256 -activated human ether-a-go-go-related gene (hERG) potassium channels are critical for the repolariza

257 nhibit the human ether-a-go-go-related gene (hERG) potassium ion channel whose inhibition is associat

258 rted compounds, and with a slightly improved hERG profile.

259 on significantly elevated total and membrane HERG protein and HERG-encoded current density by approxi

260 biquitination and proteasomal degradation of hERG protein and to an almost complete disappearance of

261 The increase in hERG protein was associated with PKC-induced phosphoryla

262 n cardiomyocytes and the expression level of hERG proteins; however, chronic (30 nM, 16 hours) PMA tr

263 rfering with Rab11 function not only delayed hERG recovery in cells after exposure to low K(+) medium

264 ation is accompanied by an increased rate of hERG recovery in the plasma membrane upon reculture foll

265 3-phosphate 5-kinase and Rab11 to facilitate hERG recycling to the plasma membrane.

266 hed acute PMA (30 nM, 30 minutes)-mediated I(hERG) reduction.

267 that beta-arrestin signaling plays a role in hERG regulation.

268 damage of hERG extends our understanding of hERG regulation.

269 encoding I(Na) and I(Kr) channels (SCN5A and hERG, respectively) are associated in defined complexes

270 its fast inactivation rate, which is key to hERG's role in cardiac action potential repolarization.

271 deep hydrophobic pockets, which may explain hERG's unusual sensitivity to many drugs.

272 ives on 50 hERG-insensitive drugs), low-cost hERG safety assay.

273 A subtle structural feature of the hERG selectivity filter might correlate with its fast in

274 highly sensitive (zero false negatives on 50 hERG-sensitive drugs) and highly specific (zero false po

275 a, we attempt to summarize new insights into hERG-specific function and articulate important unanswer

276 tics, in vivo efficacy, and selectivity over hERG, structure-activity relationship studies around the

277 In the meanwhile, the resurgent hERG tail currents are dose-dependently inhibited by AMD

278 When hERG tail currents were analyzed upon -50 mV repolarizat

279 between pairs of sigma-1 receptors bound to hERG tetramers had two peaks, at approximately 90 and ap

280 uncovered a family of positive modulators of hERG that specifically bind to the PAS domain.

281 e have determined the molecular structure of hERG to 3.8 A using cryo-electron microscopy.

282 al relevance of the unique susceptibility of hERG to proteases, we show that cardiac ischemia in a ra

283 activity, which can in turn yield simplified hERG toxicophores.

284 These findings provide novel insight into hERG trafficking and regulation.

285 le lumacaftor treatment failed to rescue the hERG trafficking defect in TSA201 cells, lumacaftor resc

286 All 3 mutations were hERG trafficking defective in iPSC-CMs.

287 Of the MICE drugs only bepridil inhibited hERG trafficking following overnight exposure.

288 ated in cardiomyocytes, where levels of both hERG transcripts were reduced by either 1a or 1b shRNA,

289 on approaches, we find that roughly half the hERG translational complexes contain SCN5A transcripts.

290 de study cohorts, pharmacological studies of HERG-type potassium channels, electrophysiological data)

291 Furthermore, although the full-length hERG variant, hERG1a, has been widely used to study hERG

292 Molecular aspects of hERG voltage-gating have been extensively studied, indic

293 However, fentanyl-mediated block of I(hERG) was voltage dependent.

294 genesis, and the recent cryoEM structure for hERG were employed.

295 (30 nM, 16 hours) PMA treatment decreased I(hERG), which became larger than untreated control I(hERG

296 ded by the human ether-a-go-go-related gene (hERG), which is important for the repolarization of the

297 ing that the sigma-1 receptor interacts with hERG with 4-fold symmetry.

298 potential (AP) was used, fentanyl blocked I(hERG) with an IC(50) of 0.3 muM.

299 hypoxia or hypokalemia additively reduced I(hERG) with fentanyl.

300 entanyl and naloxone blocked hERG current (I(hERG)) with IC(50) values of 0.9 and 74.3 muM, respectiv