Mechanisms of atrial-selective block of sodium channel by ranolazine
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چکیده
1 Mechanisms of atrial-selective block of sodium channel by ranolazine 2 I. Experimental analysis of the use-dependent block 3 4 Andrew C. Zygmunt,* Vladislav V. Nesterenko,* Sridharan Rajamani, Dan Hu, Hector 5 Barajas-Martinez, 1 Luiz Belardinelli, 2 Charles Antzelevitch 6 7 Masonic Medical Research Laboratory, Utica, NY and 2 Gilead Sciences, Inc., Palo Alto, CA 8 *V.V.N. and A.C.Z. contributed equally to this study. 9 10 Short Title: Atrial selectivity of ranolazine 11 12 Address for editorial correspondence and reprint requests: 13 Andrew C. Zygmunt, PhD 14 Masonic Medical Research Laboratory 15 2150 Bleecker St. 16 Utica, NY 13501 17 mail to: [email protected] 18 19 20 21 Articles in PresS. Am J Physiol Heart Circ Physiol (August 5, 2011). doi:10.1152/ajpheart.00242.2011
منابع مشابه
Atrial-ventricular differences in rabbit cardiac voltage-gated Na+ currents: Basis for atrial-selective block by ranolazine
BACKGROUND Class 1 antiarrhythmic drugs are highly effective in restoring and maintaining sinus rhythm in atrial fibrillation patients but carry a risk of ventricular tachyarrhythmia. The antianginal agent ranolazine is a prototypic atrial-selective voltage-gated Na+ channel blocker but the mechanisms underlying its atrial-selective action remain unclear. OBJECTIVE The present study examined ...
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Ranolazine has been shown to produce atrial-selective depression of sodium channel-dependent parameters and suppress atrial fibrillation (AF) in a variety of experimental models. The present study contrasts the effects of ranolazine and those of a clinically used anti-AF class IC agent, propafenone. Electrophysiological and anti-AF effects of propafenone and ranolazine were compared at clinical...
متن کاملAtrium-selective sodium channel block as a strategy for suppression of atrial fibrillation: differences in sodium channel inactivation between atria and ventricles and the role of ranolazine.
BACKGROUND The development of selective atrial antiarrhythmic agents is a current strategy for suppression of atrial fibrillation (AF). METHODS AND RESULTS Whole-cell patch clamp techniques were used to evaluate inactivation of peak sodium channel current (I(Na)) in myocytes isolated from canine atria and ventricles. The electrophysiological effects of therapeutic concentrations of ranolazine...
متن کاملMechanisms of atrial-selective block of Na⁺ channels by ranolazine: II. Insights from a mathematical model.
Block of Na(+) channel conductance by ranolazine displays marked atrial selectivity that is an order of magnitude higher that of other class I antiarrhythmic drugs. Here, we present a Markovian model of the Na(+) channel gating, which includes activation-inactivation coupling, aimed at elucidating the mechanisms underlying this potent atrial selectivity of ranolazine. The model incorporates exp...
متن کاملMechanisms of atrial-selective block of Na⁺ channels by ranolazine: I. Experimental analysis of the use-dependent block.
Atrial-selective inhibition of cardiac Na(+) channel current (I(Na)) and I(Na)-dependent parameters has been shown to contribute to the safe and effective management of atrial fibrillation. The present study examined the basis for the atrial-selective actions of ranolazine. Whole cell I(Na) was recorded at 15°C in canine atrial and ventricular myocytes and in human embryonic kidney (HEK)-293 ce...
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تاریخ انتشار 2011