Glycyrretinic acid blocks cardiac sodium channels expressed in Xenopus oocytes

Du, Yumin; Zhang, Songyu; Wu, Hongjin; Zou, Anruo; Lei, Ming; Cheng, Long; Liao, Yuhua

doi:10.1016/j.jep.2009.06.016

Cited by 14 publications

(13 citation statements)

References 34 publications

(38 reference statements)

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“…Treatment with 18β-GA significantly shifted the V 1/2 of activation curves in the positive direction and V 1/2 of the steady-state inactivation curves in the negative direction; these shifts were completely recovered after washout. These results confirmed and extended our previous study on GA [13] and suggested that 18β-GA alters the gating function of both WT and ΔKPQ Nav1.5 channels.…”

Section: Wwwchinapharcom Du Ym Et Alsupporting

confidence: 92%

“…For example, 18α-GA blocks voltage-gated potassium channels in vascular smooth muscle cells, while 18β-GA does not [24] . Our previous study showed that GA blocked the I Na,P mediated by the WT Nav1.5 channel (approximately 33% at 90 µmol/L) and the I Na,L mediated by the ΔKPQ Nav1.5 channel (IC 50 =67±7.08 µmol/L) [13] . In this study, 18β-GA inhibited the I Na,P mediated by the WT Nav1.5 channel with an IC 50 of 40 µmol/L and blocked I Na,P and I Na,L currents mediated by the ΔKPQ Nav1.5 channel at IC 50 values of 100 µmol/L and 37 µmol/L, respectively.…”

Section: Discussionmentioning

confidence: 91%

“…Effects of 18β-GA on HERG and Kv1.5 channels Our previous study demonstrated that GA had no significant effect on L-type calcium current (I Ca,L ) or hyperpolarizationactivated inward current (I f ) in rabbit sinoatrial node pacemaker cells [13] . In this study, we extended our previous study to investigate the effects of 18β-GA on HERG and Kv1.5 channels.…”

Section: Wwwnaturecom/aps Du Ym Et Almentioning

confidence: 95%

“…In vitro transcription of cRNAs and the isolation of oocytes were performed as previously described [13,15,16] . The plasmid pTracer-SV40 containing WT or ΔKPQ human Nav1.5 genes was a kind gift from Dr Thomas ZIMMER of Friedrich Schiller University Jena.…”

Section: In Vitro Transcription Of Crna and Functional Expression In mentioning

confidence: 99%

“…Kv1.5 conducts ultrarapid delayed rectifier current (I Kur ) in the human atria [9,10] , and the loss-of-function mutation might also result in LQTS and cardiac arrest [11] . Recently, we reported that glycyrrhetinic acid (GA), an active ingredient of licorice [12] , blocks both I NaP and I Na,L [13] . However, GA exists in two different stereoisomeric forms, the trans form and the cis form.…”

Section: Introductionmentioning

confidence: 99%

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18β-Glycyrrhetinic acid preferentially blocks late Na current generated by ΔKPQ Nav1.5 channels

Xia

Zhao

et al. 2012

Acta Pharmacol Sin

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Aim:To compare the effects of two stereoisomeric forms of glycyrrhetinic acid on different components of Na + current, HERG and Kv1.5 channel currents. Methods: Wild-type (WT) and long QT syndrome type 3 (LQT-3) mutant ∆KPQ Nav1.5 channels, as well as HERG and Kv1.5 channels were expressed in Xenopus oocytes. In addition, isolated human atrial myocytes were used. Two-microelectrode voltage-clamp technique was used to record the voltage-activated currents. Results: Superfusion of 18β-glycyrrhetinic acid (18β-GA, 1-100 μmol/L) blocked both the peak current (I Na,P ) and late current (I Na,L ) generated by WT and ΔKPQ Nav1.5 channels in a concentration-dependent manner, while 18α-glycyrrhetinic acid (18α-GA) at the same concentrations had no effects. 18β-GA preferentially blocked I Na,L (IC 50 =37.2±14.4 μmol/L) to I Na,P (IC 50 =100.4±11.2 μmol/L) generated by ∆KPQ Nav1.5 channels. In human atrial myocytes, 18β-GA (30 μmol/L) inhibited 47% of I Na,P and 87% of I Na,L induced by Anemonia sulcata toxin (ATX-II, 30 nmol/L). Superfusion of 18β-GA (100 μmol/L) had no effects on HERG and Kv1.5 channel currents. Conclusion: 18β-GA preferentially blocked the late Na current without affecting HERG and Kv1.5 channels.

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Section: Wwwchinapharcom Du Ym Et Alsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 91%

Section: Wwwnaturecom/aps Du Ym Et Almentioning

confidence: 95%

Section: In Vitro Transcription Of Crna and Functional Expression In mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

18β-Glycyrrhetinic acid preferentially blocks late Na current generated by ΔKPQ Nav1.5 channels

Xia

Zhao

et al. 2012

Acta Pharmacol Sin

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Oscillating calcium signals in smooth muscle cells underlie the persistent basal tone of internal anal sphincter

Lü

Zhang

Saur

et al. 2021

Journal Cellular Physiology

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A persistent basal tone in the internal anal sphincter (IAS) is essential for keeping the anal canal closed and fecal continence; its inhibition via the rectoanal inhibitory reflex (RAIR) is required for successful defecation. However, cellular signals underlying the IAS basal tone remain enigmatic. Here we report the origin and molecular mechanisms of calcium signals that control the IAS basal tone, using a combination approach including a novel IAS slice preparation that retains cell arrangement and architecture as in vivo, 2‐photon imaging, and cell‐specific gene‐modified mice. We found that IAS smooth muscle cells generate two forms of contractions (i.e., phasic and sustained contraction) and Ca2+ signals (i.e., synchronized Ca2+ oscillations [SCaOs] and asynchronized Ca2+ oscillations [ACaOs]) that last for hours. RyRs, TMEM16A, L‐type Ca2+ channels, and gap junctions are required for SCaOs, which account for phasic contraction and 75% of sustained contraction. Nevertheless, only RyRs are required for ACaOs, which contribute 25% of sustained contraction. Nitric oxide, the primary neurotransmitter mediating the RAIR, blocks both types of Ca2+ signals, leading to IAS's full relaxation. Our results show that the oscillating nature of Ca2+ signals generates and maintains the basal tone without causing cytotoxicity to IAS. Our study provides insight into fecal continence and normal defecation.

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Pharmacological Effects ofGlycyrrhizaspp. and Its Bioactive Constituents: Update and Review

2015

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The roots and rhizomes of various species of the perennial herb licorice (Glycyrrhiza) are used in traditional medicine for the treatment of several diseases. In experimental and clinical studies, licorice has been shown to have several pharmacological properties including antiinflammatory, antiviral, antimicrobial, antioxidative, antidiabetic, antiasthma, and anticancer activities as well as immunomodulatory, gastroprotective, hepatoprotective, neuroprotective, and cardioprotective effects. In recent years, several of the biochemical, molecular, and cellular mechanisms of licorice and its active components have also been demonstrated in experimental studies. In this review, we summarized the new phytochemical, pharmacological, and toxicological data from recent experimental and clinical studies of licorice and its bioactive constituents after our previous published review.

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Glycyrretinic acid blocks cardiac sodium channels expressed in Xenopus oocytes

Cited by 14 publications

References 34 publications

18β-Glycyrrhetinic acid preferentially blocks late Na current generated by ΔKPQ Nav1.5 channels

18β-Glycyrrhetinic acid preferentially blocks late Na current generated by ΔKPQ Nav1.5 channels

Oscillating calcium signals in smooth muscle cells underlie the persistent basal tone of internal anal sphincter

Pharmacological Effects ofGlycyrrhizaspp. and Its Bioactive Constituents: Update and Review

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