Effect of antiarrhythmic drugs on small conductance calcium - activated potassium channels.

Title Effect of antiarrhythmic drugs on small conductance calcium - activated potassium channels.
Authors R. Simó-Vicens; D.R.P. Sauter; M. Grunnet; J.G. Diness; B.H. Bentzen
Journal Eur J Pharmacol
DOI 10.1016/j.ejphar.2017.03.039
Abstract

Atrial fibrillation (AF) is the most common type of arrhythmia. Current pharmacological treatment for AF is moderately effective and/or increases the risk of serious ventricular adverse effects. To avoid ventricular adverse effects, a new target has been considered, the small conductance calcium-activated K(+) channels (KCa2.X, SK channels). In the heart, KCa2.X channels are functionally more important in atria compared to ventricles, and pharmacological inhibition of the channel confers atrial selective prolongation of the cardiac action potential and converts AF to sinus rhythm in animal models of AF. Whether antiarrhythmic drugs (AADs) recommended for treating AF target KCa2.X channels is unknown. To this end, we tested a large number of AADs on the human KCa2.2 and KCa2.3 channels to assess their effect on this new target using automated whole-cell patch clamp. Of the AADs recommended for treatment of AF only dofetilide and propafenone inhibited hKCa2.X channels, with no subtype selectivity. The calculated IC50 were 90±10µmol/l vs 60±10µmol/l for dofetilide and 42±4µmol/l vs 80±20µmol/l for propafenone (hKCa2.3 vs hKCa2.2). Whether this inhibition has clinical importance for their antiarrhythmic effect is unlikely, as the calculated IC50 values are very high compared to the effective free therapeutic plasma concentration of the drugs when used for AF treatment, 40,000-fold for dofetilide and 140-fold higher for propafenone.

Citation R. Simó-Vicens; D.R.P. Sauter; M. Grunnet; J.G. Diness; B.H. Bentzen.Effect of antiarrhythmic drugs on small conductance calcium - activated potassium channels.. Eur J Pharmacol. 2017;803:118123. doi:10.1016/j.ejphar.2017.03.039

Related Elements

Potassium

Elemental PotassiumSee more Potassium products. Potassium (atomic symbol: K, atomic number: 19) is a Block S, Group 1, Period 4 element with an atomic weight of 39.0983. The number of electrons in each of Potassium's shells is [2, 8, 8, 1] and its electron configuration is [Ar] 4s1. The potassium atom has a radius of 227.2 pm and a Van der Waals radius of 275 pm. Potassium was discovered and first isolated by Sir Humphrey Davy in 1807. Potassium is the seventh most abundant element on earth. It is one of the most reactive and electropositive of all metals and rapidly oxidizes. As with other alkali metals, potassium decomposes in water with the evolution of hydrogen because of its reacts violently with water, it only occurs in nature in ionic salts.Potassium Bohr Model In its elemental form, potassium has a silvery gray metallic appearance, but its compounds (such as potassium hydroxide) are more frequently used in industrial and chemical applications. The origin of the element's name comes from the English word 'potash,' meaning pot ashes, and the Arabic word qali, which means alkali. The symbol K originates from the Latin word kalium.

Calcium

See more Calcium products. Calcium (atomic symbol: Ca, atomic number: 20) is a Block S, Group 2, Period 4 element with an atomic weight of 40.078. The number of electrons in each of Calcium's shells is [2, 8, 8, 2] and its electron configuration is [Ar]4s2. Calcium Bohr ModelThe calcium atom has a radius of 197 pm and a Van der Waals radius of 231 pm. Calcium was discovered and first isolated by Sir Humphrey Davy in 1808. It is the fifth most abundant element in the earth's crust and can be found in minerals such as dolomite, gypsum, plagioclases, amphiboles, pyroxenes and garnets. In its elemental form, calcium has a dull gray-silver appearance. Calcium is a reactive, soft metal that is a member of the alkaline earth elements. Elemental CalciumIt frequently serves as an alloying agent for other metals like aluminum and beryllium, and industrial materials like cement and mortar are composed of calcium compounds like calcium carbonate. It is also an biologically essential substance found in teeth, bones, and shells. The name "calcium" originates from the Latin word "calics," meaning lime.