Tamulustoxin: A Novel Potassium Channel Blocker from the Venom of the Indian Red Scorpion Mesobuthus tamulus

Strong, Peter; Clark, G.S; Armugam, Arunmozhiarasi; De-Allie, F.A; Joseph, Jeremiah S.; Yemul, V; Deshpande, J.M; Kamat, R. S.; Gadre, S. V.; Gopalakrishnakone, P.; Kini, R. Manjunatha; Owen, David; Jeyaseelan, Kandiah

doi:10.1006/abbi.2000.2135

Cited by 20 publications

(12 citation statements)

References 33 publications

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“…The Indian red scorpion (Mesobuthus tamulus) causes annually a large number of deaths, especially among young children on the Indian subcontinent (19), and its venom has been a rich source for highly specific potassium channel blockers such as iberiotoxin (20) and tamulustoxin (21). We have examined the venom for the presence of other selective ion channel blockers.…”

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confidence: 99%

Tamapin, a Venom Peptide from the Indian Red Scorpion (Mesobuthus tamulus) That Targets Small Conductance Ca2+-activated K+ Channels and Afterhyperpolarization Currents in Central Neurons

Pedarzani

D’hoedt

Doorty

et al. 2002

Journal of Biological Chemistry

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The biophysical properties of small conductance Ca 2؉ -activated K ؉ (SK) channels are well suited to underlie afterhyperpolarizations (AHPs) shaping the firing patterns of a conspicuous number of central and peripheral neurons. We have identified a new scorpion toxin (tamapin) that binds to SK channels with high affinity and inhibits SK channel-mediated currents in pyramidal neurons of the hippocampus as well as in cell lines expressing distinct SK channel subunits. This toxin distinguished between the SK channels underlying the apamin-sensitive I AHP and the Ca 2؉ -activated K ؉ channels mediating the slow I AHP (sI AHP ) in hippocampal neurons. Compared with related scorpion toxins, tamapin displayed a unique, remarkable selectivity for SK2 versus SK1 (ϳ1750-fold) and SK3 (ϳ70-fold) channels and is the most potent SK2 channel blocker characterized so far (IC 50 for SK2 channels ‫؍‬ 24 pM). Tamapin will facilitate the characterization of the subunit composition of native SK channels and help determine their involvement in electrical and biochemical signaling.

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confidence: 99%

Tamapin, a Venom Peptide from the Indian Red Scorpion (Mesobuthus tamulus) That Targets Small Conductance Ca2+-activated K+ Channels and Afterhyperpolarization Currents in Central Neurons

Pedarzani

D’hoedt

Doorty

et al. 2002

Journal of Biological Chemistry

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“…Several toxins have been characterized from H. tamulus venom that block voltage-gated K v channels. Tamulustoxin (M r 3.9 kDa) (Table 2) is another toxin that was isolated on the basis of a toxin screen, this time screening the venom for toxins that inhibited 125 I-toxin I binding to rat brain synaptic plasma membranes (Strong et al 2001). Toxin I is a dendrotoxin homologue; dendrotoxins block certain voltage-gated potassium channels (K v 1.1, K v 1.2, and K v 1.6).…”

Section: Venom Constituentsmentioning

confidence: 99%

Scorpion Venom Research Around the World: Indian Red Scorpion

Strong

Mukherjee²,

Shah³

et al. 2014

Toxinology

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The Indian red scorpion is the medically most important scorpion on the Indian subcontinent, and a sting is often lethal without treatment, especially to young children. The correct identification of this species is Hottentotta tamulus; the more commonly known names, Buthus tamulus and Mesobuthus tamulus, and the suggestions of subspecies (Pocock) are incorrect and should be discouraged. Mild cases of H. tamulus envenoming show vasoconstriction and hypertension resulting from a massive release of catecholamines. Severe cases result in hypotension, pulmonary edema and myocardial dysfunction. Animal studies indicate that catecholamine release is as a consequence of prolonged sodium channel activation and potassium channel inhibition. Pulmonary edema results from many subcellular events, including kinin activation and stimulation of central serotonin receptor subtypes. Treatment with a specific antibody (with or without the a-adrenoreceptor blocker, prazosin, dependent on symptoms and clinical severity) is presently the preferred therapy. The few venom constituents that have been characterized in detail include iberiotoxin, a specific blocker of high conductance, calcium-activated potassium channels; tamapin, a specific blocker of low conductance calcium activated potassium channels (K Ca 2.2 subtype); and the short peptide insectotoxins, ButaIT and BtlTx3.

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“…In contrast no particularly specific blockers of Kv1.5 or Kv1.6 have been identified to date. Tamulustoxin (Mesobuthus tamulus) acts on Kv1.6 at 500 nM (Strong et al, 2001), but selectivity against other channels has not been determined. BmTX3 (Buthus martensii Karsch) appears to be selective for Kv4 channels, showing preference for Kv4.1 acting with an IC 50 of 105 nM (Vacher et al, 2006).…”

Section: Tityus Serrulatusmentioning

confidence: 99%

Scorpion toxin peptide action at the ion channel subunit level

Housley

Liddell

et al. 2017

Neuropharmacology

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a b s t r a c tThis review categorizes functionally validated actions of defined scorpion toxin (SCTX) neuropeptides across ion channel subclasses, highlighting key trends in this rapidly evolving field. Scorpion envenomation is a common event in many tropical and subtropical countries, with neuropharmacological actions, particularly autonomic nervous system modulation, causing significant mortality. The primary active agents within scorpion venoms are a diverse group of small neuropeptides that elicit specific potent actions across a wide range of ion channel classes. The identification and functional characterisation of these SCTX peptides has tremendous potential for development of novel pharmaceuticals that advance knowledge of ion channels and establish lead compounds for treatment of excitable tissue disorders. This review delineates the unique specificities of 320 individual SCTX peptides that collectively act on 41 ion channel subclasses. Thus the SCTX research field has significant translational implications for pathophysiology spanning neurotransmission, neurohumoral signalling, sensori-motor systems and excitation-contraction coupling.This article is part of the Special Issue entitled 'Venom-derived Peptides as Pharmacological Tools.'

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Tamulustoxin: A Novel Potassium Channel Blocker from the Venom of the Indian Red Scorpion Mesobuthus tamulus

Cited by 20 publications

References 33 publications

Tamapin, a Venom Peptide from the Indian Red Scorpion (Mesobuthus tamulus) That Targets Small Conductance Ca2+-activated K+ Channels and Afterhyperpolarization Currents in Central Neurons

Tamapin, a Venom Peptide from the Indian Red Scorpion (Mesobuthus tamulus) That Targets Small Conductance Ca2+-activated K+ Channels and Afterhyperpolarization Currents in Central Neurons

Scorpion Venom Research Around the World: Indian Red Scorpion

Scorpion toxin peptide action at the ion channel subunit level

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