PMID: 9550301Apr 29, 1998Paper

Different inhibition patterns of tedisamil for fast and slowly inactivating transient outward current in rat ventricular myocytes

Naunyn-Schmiedeberg's Archives of Pharmacology
F BergerT Weis

Abstract

Tedisamil has been described as a selective inhibitor of a fast inactivating transient outward current (i(to,f)) in rat ventricular myocytes. Because recent reports demonstrated the existence of a second slowly inactivating transient component (i(to,s)) we investigated i(to,s) and differentiated the effects of tedisamil on both transient outward current components and their influence on action potential duration. Standard electrophysiological techniques were used for whole cell recordings at 24-26 degrees C from enzymatically isolated myocytes. Inhibition of i(to,f) by tedisamil was the result of an acceleration of inactivation at positive test potentials with a concentration for half-maximal inhibition (EC50) of 4-7 micromol/l, which is confirmatory to reports from other investigators. Our new results show that i(to,s) is more sensitive to tedisamil with an EC50 of 0.5 micromol/l. Furthermore the pattern of i(to,s) inhibition is different compared with i(to,f), because inactivation of i(to,s) is not accelerated by tedisamil. Instead the amplitude of the steady state inactivation curve of i(to,s) is attenuated which indicates a reduction of maximally available current. I(to,s) was evaluated by three different methods as time-de...Continue Reading

Citations

Dec 16, 2000·Expert Opinion on Investigational Drugs·S A Doggrell
Jun 24, 2004·Expert Opinion on Investigational Drugs·Anirban Choudhury, Gregory Y H Lip
Mar 5, 2004·Expert Opinion on Investigational Drugs·Bethan Freestone, Gregory Y H Lip
Aug 19, 2003·British Journal of Pharmacology·Guilda SarrafMichael J A Walker
Oct 5, 2001·Journal of Cardiovascular Pharmacology and Therapeutics·S A Doggrell, V Nand
May 15, 2003·Journal of Cardiovascular Pharmacology and Therapeutics·Paul Dorian
May 26, 2018·Experimental Brain Research·Samuel CouthEllen Poliakoff
Jan 27, 2007·Experimental Brain Research·M ChattingtonD E Marple-Horvat
Sep 25, 2002·The Journal of Biological Chemistry·Patrick E MacDonaldMichael B Wheeler

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