Is. The Ts3 relaxes the human corpus cavernosum in vitro through the release of NO from nitrergic nerves and the elucidation of its action mechanism would be useful for the development of new therapeutic strategies to treat priapism after scorpion envenomation. Additionally, this is a molecule that can be used as a model for the development of a new drug to treat erectile dysfunction [32]. Another class of toxins that affect Nav channels is the -neurotoxins (-NaScTx), which bind to receptor site 4 in the bmjopen-2016-011824 extracellular loops that connect transmembrane segments S3 and S4 and the S1 and S2 segments in domain II [2, 18]. Thus, this class alters the voltage-dependence of channel activation to more negative potentials to cause an increased tendency to trigger the spontaneous and the repetitive potentials of the membrane [2]. Similar to NaScTx, the -neurotoxins are subdivided into four groups according to their pharmacological selectivity for insect and mammalian Nav channels: (1) m, active on mammalian Nav channels; (2) i, selectively active on insect Nav channels; (3) -like, for toxins without preference between mammalian and insect Nav channels and (4) , for those that presents a primary structure of -toxins, but with a functional -effect [14]. The toxin Ts1, a -neurotoxin with action on Nav channels, is the most abundant Methyl 2-((4-nitro-1h-pyrazol-1-yl)methyl)benzoate toxin in T. serrulatus venom, whose activities include inducing macrophage activation in vitro [33, 34]. The neurotoxins that act on voltage-gated K+ channels (Kv) can be classified into , , and [35, 36]. There are two main types of structural motifs observed in these peptide classes: (1) the common motif comprised of one or two short -helices connected to a triple-stranded antiparallel -sheet 3-Nitro-6-(trifluoromethyl)pyridin-2(1H)-one stabilized by three or four disulfide bonds, denominated CS and (2) PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/24083752 the -helix-loophelix (CS ) fold consisting of two short -helices connected by a -turn; only the kappa toxins adopt this fold [18, 37?0]. The -neurotoxins (-KTx) block the pore binding to the external vestibule of the channel and block the ionic conductivity by occlusion of the physical pore without affecting the kinetics of channel activationCordeiro et al. Journal of Venomous Animals and Toxins including Tropical Diseases (2015) 21:Page 4 ofTable 1 Examples of compounds from Tityus scorpion venomsCompounds Neurotoxins Examples Ts3, Ts5 TbTx5, Tb3 Tst3 Ts1 Ts6, Ts7 Tst26 Tt28 TdK1 Hypotensive agent Antimicrobial peptides Proteinases Hypotensin TsAP1, TsAP2 Metalloproteinase Serine PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/9544797 proteinasesa Enzymes Phospholipaseb HyaluronidaseaSpecies Tityus serrulatus Tityus bahiensis Tityus stigmurus Tityus serrulatus Tityus serrulatus Tityus stigmurus Tityus trivittatus Tityus discrepans Tityus serrulatus Tityus serrulatus Tityus serrulatus Tityus serrulatus Tityus bahiensis Tityus serrulatus Tityus stigmurus Tityus sp.Molecular Mass (kDa) 6.0?.Action Mechanism Action on Na+ channelsReferences 29?6890.9 6.0?.0 Action on K+ channels33?4 35?2.75 8.4 25.0 ?? 50.Agonist of the B(2) receptor Unclear41Lysis of the cell basement membrane 43?6 Action on coagulation factors Hydrolysis of membrane phospholipids 47 48?Catalyzes the hydrolysis of hyaluronan 50 from the extracellular matrixbIdentified in the venom, but not purified Compound found only in the transcriptome[41]. Ts6 and Ts7 from T. serrulatus, Tst26 from T. stigmurus, Tt28 from T. trivittatus and TdK1 from T. discrepans are examples of -neurotoxins that act on Kv channels [35, 42?5]. In addition to -KTxs, the venoms of.