Tremorgenic indole alkaloids potently inhibit smooth muscle high-conductance calcium-activated potassium channels

Biochemistry
H G KnausA B Smith

Abstract

Tremorgenic indole alkaloids produce neurological disorders (e.g., staggers syndromes) in ruminants. The mode of action of these fungal mycotoxins is not understood but may be related to their known effects on neurotransmitter release. To determine whether these effects could be due to inhibition of K+ channels, the interaction of various indole diterpenes with high-conductance Ca(2+)-activated K+ (maxi-K) channels was examined. Paspalitrem A, paspalitrem C, aflatrem, penitrem A, and paspalinine inhibit binding of [125I]charybdotoxin (ChTX) to maxi-K channels in bovine aortic smooth muscle sarcolemmal membranes. In contrast, three structurally related compounds, paxilline, verruculogen, and paspalicine, enhanced toxin binding. As predicted from the binding studies, covalent incorporation of [125I]ChTX into the 31-kDa subunit of the maxi-K channel was blocked by compounds that inhibit [125I]ChTX binding and enhanced by compounds that stimulate [125I]ChTX binding. Modulation of [125I]ChTX binding was due to allosteric mechanisms. Despite their different effects on binding of [125I]ChTX to maxi-K channels, all compounds potently inhibited maxi-K channels in electrophysiological experiments. Other types of voltage-dependent or Ca(2...Continue Reading

References

Nov 1, 1992·Proceedings of the National Academy of Sciences of the United States of America·R J LeonardJ P Reuben
Aug 1, 1991·Journal of Bioenergetics and Biomembranes·M L GarciaG J Kaczorowski
Jan 1, 1991·Journal of Natural Products·M I SelalaP Schepens
Mar 1, 1988·The Journal of General Physiology·R MacKinnon, C Miller
Sep 1, 1989·Drug and Chemical Toxicology·M I SelalaP J Schepens
Dec 1, 1988·Proceedings of the National Academy of Sciences of the United States of America·D L WilliamsJ P Reuben
Jan 1, 1980·Journal of Neurochemistry·P J NorrisR H Penny
Sep 1, 1982·Biochemical Pharmacology·D W PetersonP G Mantle
Aug 1, 1981·Pflügers Archiv : European journal of physiology·O P HamillF J Sigworth

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Citations

Jun 1, 1996·Journal of Bioenergetics and Biomembranes·G J KaczorowskiM L Garcia
Oct 13, 2007·Naunyn-Schmiedeberg's Archives of Pharmacology·Birgit Eichhorn, Dobromir Dobrev
Apr 11, 2006·The Journal of Membrane Biology·G GessnerS H Heinemann
Sep 3, 2008·Pflügers Archiv : European journal of physiology·Narimane Benhassine, Thomas Berger
Nov 25, 2000·European Journal of Pharmacology·C L LonglandF Michelangeli
Oct 24, 1996·European Journal of Pharmacology·F P DeFariasG Suarez-Kurtz
Nov 22, 1997·European Journal of Pharmacology·G Suarez-KurtzG J Kaczorowski
Jun 22, 1999·European Journal of Pharmacology·G Li, D W Cheung
Feb 10, 2000·European Journal of Pharmacology·E J MolinariM Gopalakrishnan
Feb 1, 2002·Toxicon : Official Journal of the International Society on Toxinology·Bing ChenYonghua Ji
Oct 29, 1998·Toxicon : Official Journal of the International Society on Toxinology·M L GarciaG J Kaczorowski
May 17, 2002·Progress in Neurobiology·Pankaj Sah, E S Louise Faber
Jan 15, 2013·Journal of the American Chemical Society·Koichi TagamiHideaki Oikawa
Dec 14, 2011·Nature Reviews. Urology·Georgi V Petkov
Dec 7, 2010·Proceedings of the National Academy of Sciences of the United States of America·Ede A Rancz, Michael Häusser
Feb 4, 1997·Proceedings of the National Academy of Sciences of the United States of America·N R HolmS Gammeltoft
Apr 5, 2005·Microcirculation : the Official Journal of the Microcirculatory Society, Inc·William F Jackson
Jan 19, 2006·The Journal of General Physiology·Jill Thompson, Ted Begenisich
Apr 28, 2010·The Journal of General Physiology·Yu ZhouChristopher J Lingle
May 19, 2007·Lymphatic Research and Biology·E A H BeckettN G McHale
Dec 1, 1994·British Journal of Pharmacology·G EdwardsA H Weston
Dec 5, 2008·Epilepsia·Jesse J SheehanAlison L Barth
Feb 11, 2003·The Journal of Physiology·Jeremy R Edgerton, Peter H Reinhart
May 15, 2012·The Journal of Pharmacology and Experimental Therapeutics·Shinichi AsanoGregory M Dick
Jan 1, 1996·Annual Review of Phytopathology·C L Schardl
Oct 16, 2012·American Journal of Physiology. Gastrointestinal and Liver Physiology·Jin ZhangDan R Halm
Sep 15, 2009·American Journal of Physiology. Heart and Circulatory Physiology·Léna BorbouseJohnathan D Tune
Mar 2, 2011·American Journal of Physiology. Heart and Circulatory Physiology·Erika B Westcott, William F Jackson
Dec 15, 2012·American Journal of Respiratory and Critical Care Medicine·Cheng-Hai ZhangRonghua ZhuGe

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