ISSN:
1540-8167
Source:
Blackwell Publishing Journal Backfiles 1879-2005
Topics:
Medicine
Notes:
Introduction: The aim of the present study was to investigate the acute action of amiodarone on the slow component of delayed rectifier K+ current (IKs) under basal conditions and during β-adrenoceptor stimulation in guinea pig ventricular myocytes. Methods and Results: Using the whole-cell patch-clamp method, IKs was evoked by depolarizing voltage-clamp steps, during superfusion with the Na+-, K+-, and Ca2+-free solution supplemented with 0.4 μM nisoldipine and 5 μM E-4031. The acute effect of amiodarone was evaluated, within ∼10 minutes after starting the bath application, by the amplitude of deactivating tail currents at –50 mV. Amiodarone concentration dependently blocked IKs and exerted a more potent effect on IKs when activated by shorter pulse durations; the degree of block by 30 μM amiodarone on IKs activated by 200 ms, 500 ms, and 2000 ms depolarizing pulses to +30 mV was 55.9 ± 5.8%, 38.6 ± 6.0%, and 27.1 ± 4.0% (n = 5 each), respectively. An envelope of tails test conducted at +10, +30, and +60 mV demonstrated that the degree of IKs block by amiodarone was gradually attenuated during membrane depolarization, which can be described by a monoexponential function, thus supporting the presence of open channel unblock. Amiodarone also blocked IKs maximally stimulated by 1 μM isoprenaline, to an extent similar to control, when IKs was activated by pulse durations of ≤2000 ms. Conclusion: We propose that amiodarone acutely blocks native IKs with characteristics associated with open channel unblock, and that the protein kinase A-mediated phosphorylation of channel proteins only minimally affects the amiodarone block.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1046/j.1540-8167.2005.40561.x
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