Margatoxin

The following drugs were used in this experiment: N^ω-nitro L-arginine methyl ester (L-NAME), indomethacin, acetylcholine hydrochloride (ACh), phenylephrine, 1H-(1, 2, 4) oxadiazole (4, 3-alpha) quinoxaline-1-one (ODQ), catalase, baicalein 18 alpha-glycyrrhetinic acid (18α-GA), ouabain, glibenclamide, barium chloride (BaCl₂), and psora-4 [5-(4-Phenylbutoxy)psoralen] (all purchased from Sigma-Aldrich Chemie GmbH, Steinheim, Germany), 17-octadecynoic acid (17-ODYA) and 1-[(2-chlorophenyl) Fdiphenylmethyl]-1H-pyrazole (TRAM-34) (Tocris Bioscience, Bristol, UK), iberiotoxin (IbTX), charybdotoxin (ChTX) and apamin (AnaSpec Inc., Fremont, CA, USA), margatoxin (MgTX), maurotoxin (MTX), α- and β-dendrotoxin (α- and β- DTX) (Alomone Labs, Jerusalem, Israel). indomethacin, ODQ, 17-ODYA, baicalein, glibenclamide and TRAM-34 were dissolved in dimethyl sulfoxide (DMSO). DMSO at ≤ 0.2% (v/v) did not influence vascular reactivity to agonists and antagonists tested, as described elsewhere73 (link). 18α-GA was dissolved in chloroform: ethanol (2:3) according to the manufacturer’s instructions and this solvent mixture did not affect the vasoreactivity (personal observation). Apamin, charybdotoxin, iberiotoxin and L-NAME were dissolved in phosphate buffer saline (PBS), whereas all other drugs were dissolved in distilled water.

DPO-1 and TTX were from Tocris (Ellisville, MO), dendrotoxin-K, hongotoxin-1, margatoxin, were from Alomone Labs (Jerusalem, Israel), while the other substances were purchased from Sigma. The recording chamber was constantly perfused with aCSF (2–3 mL/min). The treatments were applied locally using a perfusion pencil system (tip diameter 100 µm, Automate Scientific) driven by gravity. Although we have not systematically constructed dose response curves, several concentrations were tested for each drug to assess its efficacy. After these trials we have chosen for each drug the concentration that produced the maximal effect. The doses used are similar with those reported in the literature.