tailieunhanh - Báo cáo khoa học: Voltage-gated sodium channel isoform-specific effects of pompilidotoxins

Pompilidotoxins (PMTXs,a and b) are small peptides consisting of 13 amino acids purified from the venom of the solitary waspsAnoplius samari-ensis(a-PMTX) and Batozonellus maculifrons(b-PMTX). They are known to facilitate synaptic transmission in the lobster neuromuscular junction, and to slow sodium channel inactivation. | Voltage-gated sodium channel isoform-specific effects of pompilidotoxins Emanuele Schiavon1 Marijke Stevens2 Andre J. Zaharenko3 Katsuhiro Konno4 Jan Tytgat2 and Enzo Wanke1 1 Dipartimento di Biotecnologie e Bioscienze University di Milano-Bicocca Milan Italy 2 Laboratory of Toxicology University of Leuven Belgium 3 Center of Biotechnology Instituto de Pesquisas Energeticas e Nucleares Depto. de Fisiologia Instituto de Biociencias Universidade de Sao Paulo Brazil 4 Institute of NaturalMedicine University of Toyama Japan Keywords channelisoforms ion channels sodium channel inactivation toxin binding wasp toxins Correspondence E. Wanke Dipartimento di Biotecnologie e Bioscienze Universita di Milano-Bicocca Piazza della Scienza 2 20126 Milano Italy Fax 39 02 64483565 Tel 39 02 64483303 E-mail These authors contributed equally to this work Received 13 October 2009 revised 13 November 2009 accepted 4 December 2009 doi Pompilidotoxins PMTXs a and b are small peptides consisting of 13 amino acids purified from the venom of the solitary wasps Anoplius samari-ensis a-PMTX and Batozonellus maculifrons b-PMTX . They are known to facilitate synaptic transmission in the lobster neuromuscular junction and to slow sodium channel inactivation. By using b-PMTX a-PMTX and four synthetic analogs with amino acid changes we conducted a thorough study of the effects of PMTXs on sodium current inactivation in seven mammalian voltage-gated sodium channel VGSC isoforms and one insect VGSC DmNav1 . By evaluating three components of which the inactivating current is composed fast slow and steady-state components we could distinguish three distinct groups of PMTX effects. The first group concerned the insect and channels which showed a large increase in the steadystate current component without any increase in the slow component. Moreover the dose-dependent increase in this steady-state component was correlated with the .