scholarly journals Centipedes subdue giant prey by blocking KCNQ channels

2018 ◽  
Vol 115 (7) ◽  
pp. 1646-1651 ◽  
Author(s):  
Lei Luo ◽  
Bowen Li ◽  
Sheng Wang ◽  
Fangming Wu ◽  
Xiaochen Wang ◽  
...  
Keyword(s):  
Potassium Channels ◽  
Therapeutic Strategy ◽  
Nervous Systems ◽  
Kcnq Channels ◽  
Lethal Toxicity ◽  
Peptide Toxin ◽  
Scolopendra Subspinipes Mutilans ◽  
Physiological Systems

Centipedes can subdue giant prey by using venom, which is metabolically expensive to synthesize and thus used frugally through efficiently disrupting essential physiological systems. Here, we show that a centipede (Scolopendra subspinipes mutilans, ∼3 g) can subdue a mouse (∼45 g) within 30 seconds. We found that this observation is largely due to a peptide toxin in the venom, SsTx, and further established that SsTx blocks KCNQ potassium channels to exert the lethal toxicity. We also demonstrated that a KCNQ opener, retigabine, neutralizes the toxicity of a centipede’s venom. The study indicates that centipedes’ venom has evolved to simultaneously disrupt cardiovascular, respiratory, muscular, and nervous systems by targeting the broadly distributed KCNQ channels, thus providing a therapeutic strategy for centipede envenomation.

Drosophila Ortholog of Succinyl-CoA Synthetase β Subunit: A Novel Modulator of Drosophila KCNQ Channels

2008 ◽  
Vol 99 (5) ◽  
pp. 2736-2740 ◽  
Author(s):  
Lei Gao ◽  
Hong Fei ◽  
Nathan C. Connors ◽  
Jiaming Zhang ◽  
Irwin B. Levitan
Keyword(s):  
Potassium Channels ◽  
Cho Cells ◽  
Chinese Hamster ◽  
Direct Interaction ◽  
Β Subunit ◽  
Glutathione S Transferase ◽  
Kcnq Channels ◽  
Cell Surface Biotinylation ◽  
Relationship Of ◽  
Succinyl Coa Synthetase

Voltage-gated KCNQ potassium channels are responsible for slowly activating potassium currents in heart, brain, and other tissues. Functional defects of KCNQ channels are linked with many diseases, including epilepsy and cardiac arrhythmias. Therefore KCNQ potassium channels have been widely studied, especially in the CNS. We have identified Drosophila CG11963, which encodes a protein orthologous to the β subunit of mammalian succinyl-CoA synthetase (SCS, also known as succinate thiokinase), as a novel modulator of Drosophila KCNQ channels. Direct interaction of CG11963 and dKCNQ was demonstrated by yeast two-hybrid screen and coimmunoprecipitation. Cell surface biotinylation experiments further confirmed that CG11963 resides on the plasma membrane of tsA-201 cells. Coexpression of CG11963 with dKCNQ shifts the conductance–voltage ( G– V) relationship of dKCNQ channels to more positive membrane potentials in Chinese hamster ovary (CHO) cells. Moreover, directly dialyzing glutathione S-transferase fusion CG11963 protein into CHO cells also shifts the dKCNQ G– V curve rightward. The effect of CG11963 persists in the presence of 1 mM adenosine triphosphate (ATP), a substrate of SCS. Taken together, our data define CG11963 as a new dKCNQ-binding protein capable of modulating the properties of the channel. Our evidence suggests that this modulation is mediated by direct interaction of CG11963 with the channel and is not dependent on ATP.

scholarly journals Hypoxia. 3. Hypoxia and neurotransmitter synthesis

2011 ◽  
Vol 300 (4) ◽  
pp. C743-C751 ◽  
Author(s):  
Ganesh K. Kumar
Keyword(s):  
High Altitude ◽  
Intermittent Hypoxia ◽  
Sleep Disordered Breathing ◽  
Neuroendocrine Cells ◽  
Nervous Systems ◽  
Peripheral Neurons ◽  
Neurotransmitter Synthesis ◽  
Neuronal Functions ◽  
Rate Limiting ◽  
Physiological Systems

Central and peripheral neurons as well as neuroendocrine cells express a variety of neurotransmitters/modulators that play critical roles in regulation of physiological systems. The synthesis of several neurotransmitters/modulators is regulated by O2-requiring rate-limiting enzymes. Consequently, hypoxia resulting from perturbations in O2 homeostasis can affect neuronal functions by altering neurotransmitter synthesis. Two broad categories of hypoxia are frequently encountered: continuous hypoxia (CH) and intermittent hypoxia (IH). CH is often seen during high altitude sojourns, whereas IH is experienced in sleep-disordered breathing with recurrent apneas (i.e., brief, repetitive cessations of breathing). This article presents what is currently known on the effects of both forms of hypoxia on neurotransmitter levels and neurotransmitter synthesizing enzymes in the central and peripheral nervous systems.

scholarly journals Tolerance of piava juveniles to different ammonia concentrations

2015 ◽  
Vol 36 (6) ◽  
pp. 3991 ◽  
Author(s):  
Carlos Eduardo Copatti ◽  
Keide Carolina dos Santos Bolner ◽  
Felipe Link de Rosso ◽  
Vania Lucia Loro ◽  
Bernardo Baldisserotto
Keyword(s):  
Enzyme Activity ◽  
Atpase Activity ◽  
Plasma Levels ◽  
Metabolic Parameters ◽  
Fish Culture ◽  
Lethal Concentration ◽  
Protein Levels ◽  
Lethal Toxicity ◽  
Physiological Systems

The objective of this study was to evaluate the tolerance of piavas (Leporinus obtusidens) to ammonia (NH3) by measuring its effects on plasma ion levels and tissue metabolic parameters. Piava juveniles (25-30 g) were exposed to five concentrations of NH3 (mg L-1): 0.003 (control), 0.1, 0.4, 0.7, and 1.4; after 96 hours, plasma levels of Na+, K+, Cl- and NH4+ ions and metabolic and enzyme activity in tissues (liver, kidneys, gills and muscle) were measured. The lethal concentration (LC50; 96h) of NH3 was 0.27 mg L-1. As NH3 increased, Na+ and NH4+ in the plasma increased and K+ decreased. In addition, Na+/K+- ATPase activity concomitantly increased in the gills and decreased in the kidneys. Glucose, glycogen, and protein levels decreased, while lactate and ammonia increased in the tissues of piava juveniles that were treated with higher concentrations of ammonia. The observed lethal toxicity could be due to a gradual depletion of plasma ion levels and a reduction of metabolic and Na+/K+-ATPase activity in tissues. Both can lead to dysfunction in ionoregulatory and physiological systems. This finding has implications for the management of fish culture of piavas.

scholarly journals Axo-Glial Interactions Regulate the Localization of Axonal Paranodal Proteins

1999 ◽  
Vol 147 (6) ◽  
pp. 1145-1152 ◽  
Author(s):  
Jeffrey L. Dupree ◽  
Jean-Antoine Girault ◽  
Brian Popko
Keyword(s):  
Potassium Channels ◽  
Sodium Channels ◽  
Node Of Ranvier ◽  
Molecular Organization ◽  
Protein Distribution ◽  
Nervous Systems ◽  
Peripheral Nervous Systems ◽  
Axonal Protein

Mice incapable of synthesizing the abundant galactolipids of myelin exhibit disrupted paranodal axo-glial interactions in the central and peripheral nervous systems. Using these mutants, we have analyzed the role that axo-glial interactions play in the establishment of axonal protein distribution in the region of the node of Ranvier. Whereas the clustering of the nodal proteins, sodium channels, ankyrinG, and neurofascin was only slightly affected, the distribution of potassium channels and paranodin, proteins that are normally concentrated in the regions juxtaposed to the node, was dramatically altered. The potassium channels, which are normally concentrated in the paranode/juxtaparanode, were not restricted to this region but were detected throughout the internode in the galactolipid-defi- cient mice. Paranodin/contactin-associated protein (Caspr), a paranodal protein that is a potential neuronal mediator of axon-myelin binding, was not concentrated in the paranodal regions but was diffusely distributed along the internodal regions. Collectively, these findings suggest that the myelin galactolipids are essential for the proper formation of axo-glial interactions and demonstrate that a disruption in these interactions results in profound abnormalities in the molecular organization of the paranodal axolemma.

scholarly journals Centipede KCNQ Inhibitor SsTx Also Targets KV1.3

Toxins ◽  
2019 ◽  
Vol 11 (2) ◽  
pp. 76 ◽  
Author(s):  
Canwei Du ◽  
Jiameng Li ◽  
Zicheng Shao ◽  
James Mwangi ◽  
Runjia Xu ◽  
...  
Keyword(s):  
T Cells ◽  
Broad Spectrum ◽  
Selectivity Filter ◽  
Disruptive Effect ◽  
Nervous Systems ◽  
Kcnq Channels ◽  
Efficient Strategy ◽  
Kv7 Channels ◽  
Kv1.3 Channel

It was recently discovered that Ssm Spooky Toxin (SsTx) with 53 residues serves as a key killer factor in red-headed centipede’s venom arsenal, due to its potent blockage of the widely expressed KCNQ channels to simultaneously and efficiently disrupt cardiovascular, respiratory, muscular, and nervous systems, suggesting that SsTx is a basic compound for centipedes’ defense and predation. Here, we show that SsTx also inhibits KV1.3 channel, which would amplify the broad-spectrum disruptive effect of blocking KV7 channels. Interestingly, residue R12 in SsTx extends into the selectivity filter to block KV7.4, however, residue K11 in SsTx replaces this ploy when toxin binds on KV1.3. Both SsTx and its mutant SsTx_R12A inhibit cytokines production in T cells without affecting the level of KV1.3 expression. The results further suggest that SsTx is a key molecule for defense and predation in the centipedes’ venoms and it evolves efficient strategy to disturb multiple physiological targets.

KCNQ Potassium Channels as Targets of Botanical Folk Medicines

2021 ◽  
Vol 62 (1) ◽  
Author(s):  
Kaitlyn E. Redford ◽  
Geoffrey W. Abbott
Keyword(s):  
Potassium Channels ◽  
Molecular Mechanisms ◽  
Mechanisms Of Action ◽  
Plant Secondary Metabolite ◽  
Annual Review ◽  
Publication Date ◽  
Traditional Use ◽  
Kcnq Channels ◽  
Pharmacology And Toxicology ◽  
Botanical Medicines

Since prehistory, human species have depended on plants for both food and medicine. Even in countries with ready access to modern medicines, alternative treatments are still highly regarded and commonly used. Unlike modern pharmaceuticals, many botanical medicines are in widespread use despite a lack of safety and efficacy data derived from controlled clinical trials and often unclear mechanisms of action. Contributing to this are the complex and undefined composition and likely multifactorial mechanisms of action and multiple targets of many botanical medicines. Here, we review the newfound importance of the ubiquitous KCNQ subfamily of voltage-gated potassium channels as targets for botanical medicines, including basil, capers, cilantro, lavender, fennel, chamomile, ginger, and Camellia, Sophora, and Mallotus species. We discuss the implications for the traditional use of these plants for disorders such as seizures, hypertension, and diabetes and the molecular mechanisms of plant secondary metabolite effects on KCNQ channels. Expected final online publication date for the Annual Review of Pharmacology and Toxicology, Volume 62 is January 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

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