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Related Concept Videos

Antiarrhythmic Drugs: Class III Agents as Potassium Channel Blockers01:12

Antiarrhythmic Drugs: Class III Agents as Potassium Channel Blockers

Class III antiarrhythmic drugs are a group of medications that can prolong action potentials in the heart. They achieve this by blocking potassium channels or enhancing inward currents from sodium channels. However, these drugs have a unique property of "reverse use-dependence," which is most pronounced at slower heart rates and can lead to torsades de pointes—a specific type of arrhythmia. However, it is essential to note that excessive QT interval prolongation—a measure of the heart's...
Antiarrhythmic Drugs: Class I Agents as Sodium Channel Blockers01:22

Antiarrhythmic Drugs: Class I Agents as Sodium Channel Blockers

Class I antiarrhythmic drugs are used to treat various types of arrhythmias or irregular heart rhythms. These drugs block the sodium (Na+) channels in the cardiac cells, thereby affecting the movement of electrical impulses across the heart. Class I antiarrhythmic drugs are divided into three subgroups: Class IA, Class IB, and Class IC, each with distinct mechanisms of action and effects on the heart.
Class 1A Antiarrhythmic Drugs: These drugs work by moderately blocking sodium channels,...
Antiarrhythmic Drugs: Class IV Agents as Calcium Channel Blockers01:20

Antiarrhythmic Drugs: Class IV Agents as Calcium Channel Blockers

Class IV antiarrhythmic drugs, such as verapamil and diltiazem, block calcium channels. They primarily affect the heart, slowing the conduction in calcium-dependent tissues like the SA and AV nodes. These drugs manage reentrant supraventricular tachycardia (SVT) and reduce ventricular rate in atrial flutter/fibrillation.
Verapamil, a calcium channel blocker, inhibits calcium movement across myocardial cell membranes and vascular smooth muscle. This results in the dilation of coronary and...
Antiarrhythmic Drugs: Class II Agents as β-Adrenergic Blockers01:24

Antiarrhythmic Drugs: Class II Agents as β-Adrenergic Blockers

Adrenergic stimulation generally impacts cardiac rate and rhythm. Specifically, stimulation of the β-adrenoceptors triggers an increase in intracellular calcium ion influx and pacemaker currents, which may cause arrhythmias. Catecholamines like adrenaline also demonstrate β2-adrenoceptor-mediated hypokalemia, impacting cardiac action potential and disrupting the normal cardiac rhythm. Class II antiarrhythmic drugs are β-adrenoceptor antagonists or β-blockers, which indirectly block calcium...
Antiepileptic Drugs: Potassium Channel Activators01:20

Antiepileptic Drugs: Potassium Channel Activators

Ezocgabine or retigabine, an antiepileptic drug of remarkable efficacy, has revolutionized the management of seizures. It is a potassium channel activator, explicitly targeting the family of Q subtype potassium channels. It enhances the transmembrane potassium currents, regulating neuronal excitability. This action stabilizes the resting membrane potential, a pivotal factor in mitigating the hyperexcitability that characterizes epilepsy.
Ezogabine has gained approval as an adjunctive treatment...
Antihypertensive Drugs: Action of Calcium Channel Blockers01:18

Antihypertensive Drugs: Action of Calcium Channel Blockers

Calcium ions are essential to contract smooth muscle cells in blood vessels. They enter these cells through voltage-dependent calcium channels, specifically L-type calcium channels in the cell membrane. These L-type calcium channels are integral to the excitation-contraction coupling process in smooth muscle. When a stimulus is received by smooth muscle cells, their membrane depolarizes. This alteration in membrane potential instigates the opening of L-type calcium channels. As a result,...

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Amiodarone inhibits apamin-sensitive potassium currents.

Isik Turker1, Chih-Chieh Yu, Po-Cheng Chang

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Amiodarone and its metabolite desethylamiodarone inhibit the apamin-sensitive potassium current (I KAS) in human SK2 channels. This inhibition, dependent on intracellular calcium, may explain amiodarone

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Area of Science:

  • Cardiovascular Pharmacology
  • Ion Channel Physiology
  • Cardiac Electrophysiology

Background:

  • The apamin-sensitive potassium current (I KAS), mediated by SK2 channels, is crucial for action potential duration shortening in failing ventricles.
  • SK2 channel dysfunction is implicated in recurrent ventricular fibrillation (VF) in heart failure.

Purpose of the Study:

  • To investigate the hypothesis that amiodarone inhibits I KAS in human embryonic kidney 293 (HEK-293) cells expressing SK2 channels.
  • To characterize the dose- and voltage-dependence of amiodarone's effect on I KAS.
  • To assess the inhibitory effects of amiodarone's metabolite, desethylamiodarone, on I KAS.

Main Methods:

  • Utilized the patch-clamp technique to record I KAS in HEK-293 cells stably expressing human SK2 channels.
  • Administered varying concentrations of amiodarone and desethylamiodarone.
  • Assessed current inhibition under different intracellular calcium (Ca2+) concentrations and voltage potentials.

Main Results:

  • Amiodarone demonstrated dose-dependent inhibition of I KAS, with an IC50 of 2.67 ± 0.25 µM.
  • Maximal inhibition (85.6 ± 3.1%) was achieved with 50 µM amiodarone.
  • Inhibition was voltage-independent but significantly dependent on intracellular Ca2+ concentration; desethylamiodarone also inhibited I KAS in a Ca2+-dependent manner.

Conclusions:

  • Both amiodarone and desethylamiodarone inhibit I KAS at therapeutic concentrations.
  • The observed SK2 channel inhibition is independent of time and voltage but relies on intracellular Ca2+ levels.
  • This I KAS inhibition may contribute to amiodarone's efficacy in preventing electrical storm in failing hearts.