REAL

Pharmacological block of the slow component of the outward delayed rectifier current (IKs) fails to lengthen rabbit ventricular muscle QTcand action potential duration

Lengyel, Csaba Attila and Iost, Norbert and Virág, László and Varró, András and Lathrop, David A. and Papp, Julius Gyula (2001) Pharmacological block of the slow component of the outward delayed rectifier current (IKs) fails to lengthen rabbit ventricular muscle QTcand action potential duration. British Journal of Pharmacology, 132 (1). pp. 101-110. ISSN 0007-1188

[img] Text
1109515.PDF
Restricted to Registered users only

Download (204kB) | Request a copy

Abstract

1 The effects of I-Ks block by chromanol 293B and L-735,821 on rabbit QT-interval, action potential duration (APD), and membrane current were compared to those of E-4031, a recognized I-Kr blocker. Measurements were made in rabbit Langendorff-perfused whole hearts, isolated papillary muscle, and single isolated ventricular myocytes. 2 Neither chromanol 293B (10 muM) nor L-735,821 (100 nM) had a significant effect on QTc interval in Langendorff-perfused hearts. E-4031 (100 nM), on the other hand, significantly increased QTc interval (35.6 +/- 3.9%, n = 8, P < 0.05). 3 Similarly both chromanol 293B (10 <mu>M) and L-735,821 (100 nM) produced little increase in papillary muscle APD (less than 7%) while pacing at cycle lengths between 300 and 5000 ms. In contrast, E-4031 (100 nM) markedly increased (30-60%) APD in a reverse frequency-dependent manner. 4 In ventricular myocytes, the same concentrations of chromanol 293B (10 muM), L-735,821 (100 nM) and E-4031 (1 muM) markedly or totally blocked I-Ks and I-Kr, respectively. 5 I-Ks tail currents activated slowly (at + 30 mV, tau = 885.1 +/- 48.2 ms, n = 21) and deactivated rapidly (at -40 mV, tau = 157.1+/-4.7 ms, n = 22), while IKr tail currents activated rapidly (at +30 mV, tau = 35.5 +/- 3.1 ms, n = 26) and deactivated slowly (at -40 mV, tau (1) = 641.5 +/- 29.0 ms, tau (2) = 6531 +/- 343, n = 35). I-Kr, was estimated to contribute substantially more to total current density during normal ventricular muscle action potentials (i.e., after a 150 ms square pulse to + 30 mV) than does I-Ks 6 These findings indicate that block of I-Ks is not likely to provide antiarrhythmic benefit by lengthening normal ventricular muscle QTc, APD, and refractoriness over a wide range of frequencies.

Item Type: Article
Subjects: R Medicine / orvostudomány > RM Therapeutics. Pharmacology / terápia, gyógyszertan
R Medicine / orvostudomány > RS Pharmacy and materia medica / gyógyszerészet, gyógyászati eszközök
Depositing User: Erika Bilicsi
Date Deposited: 12 Mar 2013 13:16
Last Modified: 12 Mar 2013 13:16
URI: http://real.mtak.hu/id/eprint/4397

Actions (login required)

Edit Item Edit Item