Extra- and intracellular action of quaternary devapamil on muscle L-type Ca(2+)-channels

British Journal of Pharmacology
S BerjukovJ Striessnig

Abstract

1. The quaternary derivative of the potent verapamil-analogue, (-)-D888, (qD888, 4-cyano-4-(3,4-dimethoxyphenyl)-N-[2-(3-methoxy phenyl)ethyl]-N,N,5-trimethyl-1-hexanaminium) was synthesized as a novel membrane-impermeable probe to study the localization of phenylalkylamine (PAA) effector domains on L-type Ca2+ channels. Channel block by qD888 was investigated in smooth muscle-like (A7r5) cells after extra- and intracellular application by use of the whole-cell configuration of the patch clamp technique. 2. Extracellularly applied qD888 inhibited Sr2+ (Isr) (IC50 = 90 microM) and Na+ (IC50 = 27 microM) inward currents through L-type Ca(2+)-channels mainly in a resting-state-dependent manner. Structurally closely related quaternary PAAs (e.g. D890) were ineffective after extracellular application. 3. QD888 also blocked Isr from the cytoplasmic side, as did other quaternary PAAs (D890, D575). Intracellular block was clearly dependent on channel opening, which resulted in pronounced use-dependence. 4. We conclude that qD888 blocks L-type Ca2+ channels not only from the intracellular side, via interaction with the classical PAA binding domain, but also from the extracellular channel surface. The properties of Ca2+ channel block tog...Continue Reading

References

Jun 1, 1992·Trends in Pharmacological Sciences·W A Catterall, J Striessnig
Jan 1, 1990·Reviews of Physiology, Biochemistry and Pharmacology·H Glossmann, J Striessnig
Mar 3, 1986·FEBS Letters·J StriessnigH Glossmann
Jan 1, 1985·Methods in Enzymology·H Glossmann, D R Ferry
Nov 4, 1986·European Journal of Pharmacology·E J White, H F Bradford
Aug 1, 1981·Pflügers Archiv : European journal of physiology·O P HamillF J Sigworth
Jun 1, 1982·Pflügers Archiv : European journal of physiology·J HeschelerW Trautwein
May 15, 1984·European Journal of Biochemistry·A GollH Glossmann
Jan 1, 1995·Pflügers Archiv : European journal of physiology·A SavchenkoS Hering
Sep 22, 1995·The Journal of Biological Chemistry·G H HockermanW A Catterall
Mar 1, 1993·Japanese Journal of Pharmacology·S Adachi-AkahaneT Nagao
Sep 1, 1995·Naunyn-Schmiedeberg's Archives of Pharmacology·J W Wegener, H Nawrath
May 17, 1996·The Journal of Biological Chemistry·F DöringH Glossman

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Citations

Dec 16, 1998·Trends in Pharmacological Sciences·S HeringE N Timin
Nov 7, 1998·British Journal of Pharmacology·S AczélS Hering
Dec 16, 1997·Proceedings of the National Academy of Sciences of the United States of America·S HeringE N Timin
Aug 25, 2009·The Journal of Biological Chemistry·Ricky C K ChengBoris S Zhorov
Dec 15, 2010·Molecular Pharmacology·Pamela BergsonDorothy A Hanck
Oct 25, 2011·Channels·Gregory M LipkindDorothy A Hanck
Oct 27, 2010·British Journal of Pharmacology·W ShabbirS Hering

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