Solution structure of Jingzhaotoxin-III, a peptide toxin inhibiting both Nav1.5 and Kv2.1 channels

Liao, Zhi-Min; Yuan, Chunhua; Peng, Kuan; Xiao, Yucheng; Liang, Songping

doi:10.1016/j.toxicon.2007.03.006

Cited by 23 publications

(30 citation statements)

References 22 publications

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“…Recent studies confirmed by polymerase chain reaction (data not shown) have indicated that Kv2.1 is a major component of cortical neuron I K channels (Guan et al, 2007). In the present study, we report that inhibition of Kv2.1 ␣-subunits using a specific toxin (JZTX-III) reported to selectively block Kv2.1 ␣-subunits (Liao et al, 2007) eliminated the inhibitory effect of amoxapine on I K , implying that Kv2.1 ␣-subunits are central to amoxapine inhibition. We also report that JZTX-III significantly reduced I K amplitudes in cortical neurons, arguing that Kv2.1 ␣-subunits are an integral part of cortical I K channels.…”

Section: Amoxapine Inhibited I K 443supporting

confidence: 61%

“…In particular, subunit Kv2.1, which is expressed at high levels in most mammalian central neurons, is a major contributor to I K channels and plays a crucial role in regulating neuronal excitability (Murakoshi and Trimmer, 1999;Du et al, 2000). To address the potential role of Kv2.1 in amoxapine inhibition of I K channel activity, we used JZTX-III, a toxin known to specifically eliminate the Kv2.1 subunit (Liao et al, 2007). To confirm the selectivity of JZTX-III, experiments were first carried out in HEK293 cells transfected with an expression vector encoding the Kv2.1 ␣-subunit.…”

Section: Amoxapine Inhibited I K 441mentioning

confidence: 99%

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Amoxapine Inhibits the Delayed Rectifier Outward K+ Current in Mouse Cortical Neurons via cAMP/Protein Kinase A Pathways

He¹,

Zhan²,

Yang³

et al. 2010

The Journal of Pharmacology and Experimental Therapeutics

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Ion channels are known to be modulated by antidepressant drugs, but the molecular mechanisms are not known. We have shown that the antidepressant drug amoxapine suppresses rectifier outward K ϩ (I K ) currents in mouse cortical neurons. At a concentration of 10 to 500 M, amoxapine reversibly inhibited I K in a dose-dependent manner and modulated both steady-state activation and inactivation properties. The application of forskolin or dibutyryl cAMP mimicked the inhibitory effect of amoxapine on I K and abolished further inhibition by amoxapine. N- ethyl]-5-iso-quinolinesulphonamide (H-89), a protein kinase A (PKA) inhibitor, augmented I K amplitudes and completely eliminated amoxapine inhibition of I K . Amoxapine was also found to significantly increase intracellular cAMP levels. The effects of amoxapine on I K were abolished by preincubation with 5-hydroxytryptamine (5-HT) and the antagonists of 5-HT 2 receptor. Moreover, intracellular application of guanosine 5Ј-[␥thio]-triphosphate increased I K amplitudes and prevented amoxapine-induced inhibition. The selective Kv2.1 subunit blocker Jingzhaotoxin-III reduced I K amplitudes by 30% and also significantly abolished the inhibitory effect of amoxapine. Together these results suggest that amoxapine inhibits I K in mouse cortical neurons by cAMP/PKA-dependent pathway associated with the 5-HT receptor, and suggest that the Kv2

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Section: Amoxapine Inhibited I K 443supporting

confidence: 61%

Section: Amoxapine Inhibited I K 441mentioning

confidence: 99%

Amoxapine Inhibits the Delayed Rectifier Outward K+ Current in Mouse Cortical Neurons via cAMP/Protein Kinase A Pathways

He¹,

Zhan²,

Yang³

et al. 2010

The Journal of Pharmacology and Experimental Therapeutics

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“…Hm-3 Molecule Is Amphiphilic-All sodium channel activation inhibitors from spiders with a known three-dimensional structure present a Janus-faced molecular surface (23,42,49) (Fig. 3C), and analysis of Hm-3 spatial structure has shown that it is not an exception.…”

Section: Hm-3 Shares Low Homology But Similar Fold Withmentioning

confidence: 99%

Structure of Membrane-active Toxin from Crab Spider Heriaeus melloteei Suggests Parallel Evolution of Sodium Channel Gating Modifiers in Araneomorphae and Mygalomorphae

Berkut

Peigneur

Myshkin

et al. 2015

Journal of Biological Chemistry

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Background: Several toxins from mygalomorph spiders are known to inhibit sodium channel activation. Results: Hm-3 toxin from the araneomorph spider Heriaeus melloteei inhibits mammalian and insect sodium channel activation and possesses membrane activity. Conclusion: Hm-3 binds to sodium channel voltage sensors through membrane access. Significance: The first sodium channel activation inhibitor from Araneomorphae points to parallel evolution of H. melloteei and its distant mygalomorph relatives.

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“…In the presence of the K þ -channel blocker, TEA (10 mM), the TGF-b1-induced increase in GABA A receptor a6 subunit mRNA levels was abolished (1.3 AE 8.0%, P > 0.2). In addition, Jingzhaotoxin-III (JZTX-III), a toxin known to specifically eliminate Kv2.1 channel activity (Liao et al, 2007) significantly reduced TGF-b1-induced increase in GABA A receptor a6 subunit mRNA levels (2 AE 2.0%, P > 0.2), suggesting that the effects of TGF-b1 on GABA subunit expression are mediated via its effects on Kv2.1-mediated I K currents.…”

Section: Journal Of Cellular Physiologymentioning

confidence: 99%

TGF‐β1 enhances Kv2.1 potassium channel protein expression and promotes maturation of cerebellar granule neurons

Zhuang¹,

Wang²,

Zhou³

et al. 2011

Journal Cellular Physiology

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Members of the transforming growth factor-β (TGF-β) family of cytokines are involved in diverse physiological processes. Although TGF-β is known to play multiple roles in the mammalian central nervous system (CNS), its role in neuronal development has not been explored. We have studied the effects of TGF-β1 on the electrophysiological properties and maturation of rat primary cerebellar granule neurons (CGNs). We report that incubation with TGF-β1 increased delayed rectifier potassium current (I(K) ) amplitudes in a dose- and time-dependent manner, but did not affect the kinetic properties of the channel. Exposure to TGF-β1 (20 ng/ml) for 36 h led to a 37.2% increase in I(K) amplitudes. There was no significant change in mRNA levels for the key Kv2.1 channel protein, but translation blockade abolished the increase in protein levels and channel activity, arguing that TGF-β1 increases I(K) amplitudes by upregulating translation of the Kv2.1 channel protein. Although TGF-β1 treatment did not affect the activity of protein kinase A (PKA), and constitutive activation of PKA with forskolin failed to increase I(K) amplitudes, inhibition of PKA prevented channel upregulation, demonstrating that basal PKA activity is required for TGF-β1 stimulation of I(K) channel activity. TGF-β1 also promoted the expression of the γ-aminobutyric acid (GABA(A) ) receptor α6 subunit, a marker of mature CGNs, and calcium influx during depolarizing stimuli was reduced by TGF-β1. The effects of TGF-β1 were only observed during a narrow developmental time-window, and were lost as CGNs matured. These findings suggest that TGF-β1 upregulates K(+) channel expression and I(K) currents and thereby promotes CGN maturation.

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Solution structure of Jingzhaotoxin-III, a peptide toxin inhibiting both Nav1.5 and Kv2.1 channels

Cited by 23 publications

References 22 publications

Amoxapine Inhibits the Delayed Rectifier Outward K+ Current in Mouse Cortical Neurons via cAMP/Protein Kinase A Pathways

Amoxapine Inhibits the Delayed Rectifier Outward K+ Current in Mouse Cortical Neurons via cAMP/Protein Kinase A Pathways

Structure of Membrane-active Toxin from Crab Spider Heriaeus melloteei Suggests Parallel Evolution of Sodium Channel Gating Modifiers in Araneomorphae and Mygalomorphae

TGF‐β1 enhances Kv2.1 potassium channel protein expression and promotes maturation of cerebellar granule neurons

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