Get 20M+ Full-Text Papers For Less Than $1.50/day. Start a 7-Day Trial for You or Your Team.

Learn More →

Effects of propafenone and 5‐hydroxy‐propafenone on hKv1.5 channels

Effects of propafenone and 5‐hydroxy‐propafenone on hKv1.5 channels 1 The goal of this study was to analyse the effects of propafenone and its major metabolite, 5‐hydroxy‐propafenone, on a human cardiac K+ channel (hKv1.5) stably expressed in Ltk− cells and using the whole‐cell configuration of the patch‐clamp technique. 2 Propafenone and 5‐hydroxy‐propafenone inhibited in a concentration‐dependent manner the hKv1.5 current with KD values of 4.4±0.3 μM and 9.2±1.6 μM, respectively. 3 Block induced by both drugs was voltage‐dependent consistent with a value of electrical distance (referenced to the cytoplasmic side) of 0.17±0.55 (n=10) and 0.16±0.81 (n=16). 4 The apparent association (k) and dissociation (l) rate constants for propafenone were (8.9±0.9)×106 M−1 s−1 and 39.5±4.2 s−1, respectively. For 5‐hydroxy‐propafenone these values averaged (2.3±0.3)×106 M−1 s−1 and 21.4±3.1 s−1, respectively. 5 Both drugs reduced the tail current amplitude recorded at −40 mV after 250 ms depolarizing pulses to +60 mV, and slowed the deactivation time course resulting in a ‘crossover’ phenomenon when the tail currents recorded under control conditions and in the presence of each drug were superimposed. 6 Both compounds induced a small but statistically significant use‐dependent block when trains of depolarizations at frequencies between 0.5 and 3 Hz were applied. 7 These results indicate that propafenone and its metabolite block hKv1.5 channels in a concentration‐, voltage‐, time‐ and use‐dependent manner and the concentrations needed to observe these effects are in the therapeutical range. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png British Journal of Pharmacology Wiley

Effects of propafenone and 5‐hydroxy‐propafenone on hKv1.5 channels

Download PDF
10 pages

Loading next page...
 
/lp/wiley/effects-of-propafenone-and-5-hydroxy-propafenone-on-hkv1-5-channels-pNgEVMLxxR

References (61)

Publisher
Wiley
Copyright
"Copyright © 1998 Wiley Subscription Services, Inc., A Wiley Company"
ISSN
0007-1188
eISSN
1476-5381
DOI
10.1038/sj.bjp.0702129
pmid
9846634
Publisher site
See Article on Publisher Site

Abstract

1 The goal of this study was to analyse the effects of propafenone and its major metabolite, 5‐hydroxy‐propafenone, on a human cardiac K+ channel (hKv1.5) stably expressed in Ltk− cells and using the whole‐cell configuration of the patch‐clamp technique. 2 Propafenone and 5‐hydroxy‐propafenone inhibited in a concentration‐dependent manner the hKv1.5 current with KD values of 4.4±0.3 μM and 9.2±1.6 μM, respectively. 3 Block induced by both drugs was voltage‐dependent consistent with a value of electrical distance (referenced to the cytoplasmic side) of 0.17±0.55 (n=10) and 0.16±0.81 (n=16). 4 The apparent association (k) and dissociation (l) rate constants for propafenone were (8.9±0.9)×106 M−1 s−1 and 39.5±4.2 s−1, respectively. For 5‐hydroxy‐propafenone these values averaged (2.3±0.3)×106 M−1 s−1 and 21.4±3.1 s−1, respectively. 5 Both drugs reduced the tail current amplitude recorded at −40 mV after 250 ms depolarizing pulses to +60 mV, and slowed the deactivation time course resulting in a ‘crossover’ phenomenon when the tail currents recorded under control conditions and in the presence of each drug were superimposed. 6 Both compounds induced a small but statistically significant use‐dependent block when trains of depolarizations at frequencies between 0.5 and 3 Hz were applied. 7 These results indicate that propafenone and its metabolite block hKv1.5 channels in a concentration‐, voltage‐, time‐ and use‐dependent manner and the concentrations needed to observe these effects are in the therapeutical range.

Journal

British Journal of Pharmacology – Wiley

Published: Nov 1, 1998

Keywords: ; ;

There are no references for this article.