The Venom of <i>Ornithoctonus huwena</i> affect the electrophysiological stability of neonatal rat ventricular myocytes by inhibiting sodium, potassium and calcium current

Yan, Sha; Huang, Pengfei; Wang, Ying; Zeng, Xin; Zhang, Yiya

doi:10.1080/19336950.2018.1449497

Cited by 3 publications

(3 citation statements)

References 34 publications

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“…Neonatal rat ventricular myocytes cells were obtained from ventricles of neonatal Sprague–Dawley rats as previously reported (Sung et al, 2012; Yan et al, 2018). SD rats (Hunan SJA Laboratory Animal Co., Ltd., Changsha, China) were used according to the guidelines of the National Institutes of Health for Care and Use of Laboratory Animals.…”

Section: Methodsmentioning

confidence: 99%

JZTX-V Targets the Voltage Sensor in Kv4.2 to Inhibit Ito Potassium Channels in Cardiomyocytes

Zhang

Luo

et al. 2019

Front. Pharmacol.

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Kv4 potassium channels are responsible for transient outward K + currents in the cardiac action potential (AP). Previous experiments by our group demonstrated that Jingzhaotoxin-V (JZTX-V) selectively inhibits A-type potassium channels. However, the specific effects of JZTX-V on the transient outward (I to ) current of cardiomyocytes and underlying mechanism of action remain unclear. In the current study, 100 nM JZTX-V effectively inhibited the I to current and extended the action potential duration (APD) of neonatal rat ventricular myocytes (NRVM). We further analyzed the effects of JZTX-V on Kv4.2, a cloned channel believed to underlie the I to current in rat cardiomyocytes. JZTX-V inhibited the Kv4.2 current with a half-maximal inhibitory concentration (IC 50 ) of 13 ± 1.7 nM. To establish the molecular mechanism underlying the inhibitory action of JZTX-V on Kv4.2, we performed alanine scanning mutagenesis of Kv4.2 and JZTX-V and assessed the effects of the mutations on binding activities of the proteins. Interestingly, the Kv4.2 mutations V285A, F289A, and V290A reduced the affinity for JZTX-V while I275A and L277A increased the affinity for JZTX-V. Moreover, mutation of positively charged residues (R20 and K22) of JZTX-V and the hydrophobic patch (formed by W5, M6, and W7) led to a significant reduction in toxin sensitivity, indicating that the hydrophobic patch and electrostatic interactions played key roles in the binding of JZTX-V with Kv4.2. Data from our study have shed light on the specific roles and molecular mechanisms of JZTX-V in the regulation of I to potassium channels and supported its utility as a potential novel antiarrhythmic drug.

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Section: Methodsmentioning

confidence: 99%

JZTX-V Targets the Voltage Sensor in Kv4.2 to Inhibit Ito Potassium Channels in Cardiomyocytes

Zhang

Luo

et al. 2019

Front. Pharmacol.

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“…The venom was collected from adult female H. hainanum using an electro-pulse stimulator as described previously (Hu et al, 2014;Yan et al, 2018). Expelled venom was collected from the fang tips with a tube, pooled, and freeze-dried.…”

Section: Spider Venom and Treatmentmentioning

confidence: 99%

“…The solidum currents in HaCaT and fibroblast cells were detected using the whole-cell patch-clamp technique (Axon 700B patch-clamp, Irvine, CA, USA) as previously described (Yan et al, 2018). To detect voltage-gated Nav currents, we used an extracellular solution containing (in mM): 145 NaCl, 1.5 CaCl 2 , 2 MgCl 2 , 2.5 KCl, 10 D-glucose and 10 HEPES, (pH 7.4).…”

Section: Patch Clampmentioning

confidence: 99%

Haplopelma hainanum venom induces inflammatory skin lesions

Deng

Wang

Shi

et al. 2020

PeerJ

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The Haplopelma hainanum is a species of theraphosid spider from China. Its large size and charming appearance make this species a popular pet. According to a previous study, theraphosid spider bites can induce pain, erythema, and edema in humans and can present more severely in domestic animals. The pathological consequences of envenomation by H. hainanum remain unclear. In this study, we investigated the effects and mechanisms of H. hainanum envenomation in mice. We showed that the venom induced slight swelling, intense inflammatory response, and increased the microvascular density in mice skin. Moreover, we found that 50 µg/ml of the spider’s venom induced IL-1β expression in both HaCaT cells and fibroblast cells, but repressed CXCL10 expression in fibroblasts. The venom significantly induced cell senescence and repressed cell proliferation and migration in both HaCaT cells and fibroblast cells. Finally, we examined the expression of Nav channel in HaCaT and fibroblast cells and found that H. hainanum venom effectively inhibited Na+ currents in HaCaT cells. Our study calls for further investigation of the pathological consequences and potential mechanisms of H. hainanum envenomation. This information might assist in the development of suitable therapy.

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Species-dependent differences in the inhibition of various potassium currents and in their effects on repolarization in cardiac ventricular muscle

Árpádffy-Lovas

Mohammed

Naveed

et al. 2022

Can. J. Physiol. Pharmacol.

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Even though rodents are accessible model animals, their electrophysiological properties are deeply different from that of human, making the translation of rat studies to human rather difficult. We compared the mechanisms of ventricular repolarization in various animal models to those of human by measuring cardiac ventricular action potentials from ventricular papillary muscle preparations using conventional microelectrodes, and applying selective inhibitors of various potassium transmembrane ion currents. Inhibition of the IK1 current (10 µM barium chloride) significantly prolonged rat ventricular repolarization, but only slightly prolonged it in dog, and did not affect it in human. On the contrary, IKr inhibition (50 nM dofetilide) significantly prolonged repolarization in human, rabbit, and dog, but not in rat. Inhibition of the IKur current (1 µM XEN-D0101) only prolonged rat ventricular repolarization, and had no effect in human or dog. Inhibition of the IKs (500 nM HMR-1556) and Ito currents (100 µM chromanol-293B) elicited similar effects in all investigated species. We conclude that dog ventricular preparations have the strongest, and rat ventricular preparations have the weakest translational value in cardiac electrophysiological experiments.

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The Venom of Ornithoctonus huwena affect the electrophysiological stability of neonatal rat ventricular myocytes by inhibiting sodium, potassium and calcium current

Cited by 3 publications

References 34 publications

JZTX-V Targets the Voltage Sensor in Kv4.2 to Inhibit Ito Potassium Channels in Cardiomyocytes

JZTX-V Targets the Voltage Sensor in Kv4.2 to Inhibit Ito Potassium Channels in Cardiomyocytes

Haplopelma hainanum venom induces inflammatory skin lesions

Species-dependent differences in the inhibition of various potassium currents and in their effects on repolarization in cardiac ventricular muscle

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