Novel Tarantula Toxins for Subtypes of Voltage-Dependent Potassium Channels in the Kv2 and Kv4 Subfamilies

Abstract

Three novel peptides with the ability to inhibit voltage-dependent potassium channels in the shab (Kv2) and shal (Kv4) subfamilies were identified from the venom of the African tarantulas Stromatopelma calceata (ScTx1) and Heteroscodra maculata (HmTx1, HmTx2). The three toxins are 34-to 38-amino acid peptides that belong to the structural family of inhibitor cystine knot spider peptides reticulated by three disulfide bridges. Electrophysiological recordings in COS cells show that these toxins act as gating modifier of voltage-dependent K ϩ channels. ScTx1 is the first high-affinity inhibitor of the Kv2.2 channel subtype (IC 50 , 21.4 nM) to be described. ScTx1 also inhibits the Kv2.1 channels, with an IC 50 of 12.7 nM, and Kv2.1/Kv9.3 heteromultimers that have been proposed to be involved in O 2 sensing in pulmonary artery myocytes. In addition, it is the most effective inhibitor of Kv4.2 channels described thus far, with an IC 50 of 1.2 nM. HmTx toxins share sequence similarities with both the potassium channel blocker toxins (HmTx1) and the calcium channel blocker toxin -GsTx

Postnatal development of A-type and Kv1- and Kv2-mediated potassium channel currents in neocortical pyramidal neurons

“…ScTx has similar affinity for Kv2 subunits and Kv4 subunits (Escoubas et al 2002). Thus in most cells the rising phase of the ScTx-sensitive outward current (tested in the presence of DTX, MTX, and 100 M CdCl 2 ) was steeper than expected for Kv2-mediated current alone (e.g., Fig.…”

“…At this dose, ScTx also blocks A-type current in most cells (see below). The ScTx block is voltage dependent, with unblocking occurring at potentials more depolarized than approximately ϩ10 mV (Escoubas et al 2002;Guan et al 2007b).…”

“…Putative Kv2-mediated current was defined as the current sensitive to 600 nM stromatoxin (ScTx; Escoubas et al 2002). ScTx inhibits the Kv2 subunit-mediated current in pyramidal neurons with an IC 50 of 160 nM (Guan et al 2007b).…”

A verified bite by Heteroscodra maculata (Togo starburst or ornamental baboon tarantula) resulting in long-lasting muscle cramps

“…One toxin in their venom, heteroscodratoxin 1 (HmTx1), has been found to inhibit voltage-dependent potassium channels (the Kv2.2-subtype found in neurons in the brain) and immediately induce convulsions in mice. Death occurred in less than one hour after injection of 500pmol [4]. Injection of a lower dose (100 pmol) induced rapid convulsions (within 3 minutes), spasms, and tremors, with death occurring in less than two hours and being preceded by recurrent spasms and paralysis [4].…”

“…Death occurred in less than one hour after injection of 500pmol [4]. Injection of a lower dose (100 pmol) induced rapid convulsions (within 3 minutes), spasms, and tremors, with death occurring in less than two hours and being preceded by recurrent spasms and paralysis [4]. There is no literature to be found on bites by H. maculata, but in the very few bite reports found online in spider forums [5], only a minority developed muscle cramps, lasting no longer than a few days, the sensation being described as comparable to feeling sore after intense exercise.…”