Sophion Bioscience

hERG
human ether-a-go-go related gene potassium channel

(Alternative nomenclature: KCNH2, K_v11.1, erg1, LQT2)

hERG is a voltage-gated 6-TM 1-P type potassium channel. Homotetrameric. Important for repolarization of cardiac myocytes upon passage of an action potential. Highly susceptible to a multitude of chemical compounds. Important target for safety studies of new therapeutical compounds.

Localization:
Cardiac myocytes

Information link:
http://www.expasy.org/cgi-bin/niceprot.pl?Q02280

QPatch recording of hERG currents:

QPatch whole-cell currents traces (one trace is highlighted). Voltage protocol: 10 ms at - 90mV (holding potential), 20 ms at -50 mV, 1920 ms at +20mV and 2000 ms at -50 mV. Expression system: CHO.

Pharmacological profiling:
Inhibitors: Astemizole, Azimilide, Bepridil, Cisapride, Chlorpromazine, Dofetilide, d-Sotalol, E-4031, Flecainide, Fluoxetin, Haloperidol, MK-499, Pimozide, Propafenone, Quinidine, rBe-Km1, Tamofene, Terfenadine, Verapamil

Activators: NS1643, RPR260243
(The lists are not intended to be complete)

QPatch concentration - response analysis:

QPatch test of propafenone. Four increasing concentrations (0.1-100 μM) were applied to CHO cells expressing hERG. I-t plot for peak tail currents. Red, green and blue points represent measured currents, leak currents and leak-corrected currents, respectively.

Concentration-response plot based on the currents shown in the I-t plot

Test study comprising 9 known reference compounds. X-axis: IC₅₀ values from manual patch-clamp. Y-axis: IC₅₀ values from QPatch

Test study comprising 16 know reference compounds. X-axis: IC₅₀ values from manual patch-clamp. Y-axis: IC₅₀ values from QPatch

Pathophysiology:
cardiac arrhythmias (LQT syndrome, torsade des pointe), cardiac arrest