Consequences of antiarrhythmic drugs on HCN4 channel current

Outcomes of antiarrhythmic drugs on HCN4 channel currents in HEK293 cells Effects of class Ia antiarrhythmic drugs, quinidine, disopyramide, and cibenzoline, on the HCN4 channel current were examined in HEK293 cells. Quinidine created a small reduction of the HCN4 channel current in a concentration of 30 uM. The calculated IC50 value of quinidine for inhibiting the channel current Canagliflozin msds was 78. 3 uM, that was higher than the therapeutic concentration of quinidine. Disopyramide and cibenzoline also inhibited the HCN4 channel current weakly, with determined IC50 values of 46. 249 and 8 uM, respectively, which were both greater than the therapeutic concentrations. Effects of class Ib antiarrhythmic drugs, lidocaine, mexiletine, and aprindine, on the HCN4 channel current were also examined in HEK293 cells. Lidocaine at a focus Neuroendocrine tumor of 30 uM inhibited the HCN4 channel current, especially at hyperpolarizing voltages below 100 mV. The inhibitory effect of lidocaine around the current at 70 mV was minimal and the calculated IC50 value was 276 uM. Mexiletine and aprindine also weakly inhibited the HCN4 channel current. The determined IC50 values of mexiletine and aprindine for curbing the HCN4 channel current were 43 and 309. 7 uM, respectively. The IC50 values of class Ib drugs on HCN4 channels were higher when compared with the therapeutic concentrations. On HCN4 channel current in HEK293 cells, we also examined effects of class Ic anti-arrhythmic medications, flecainide and propafenone. Propafenone in a concentration of 30 uM reasonably inhibited the HCN4 channel current, having a determined IC50 value of 14. 3 uM, which was relatively near to the therapeutic concentration of propafenone. However, the inhibitory effect of flecainide on the HCN4 channel current was quite weak and the calculated pifithrin IC50 value was 1700 uM, which was higher compared to the concentration. Impact of the class II antiarrhythmic drug propranolol to the HCN4 channel current was analyzed. The calculated IC50 value of propranolol for suppressing the HCN4 channel current was 50. 5 uM, which was also greater compared to the concentration. Effect of class III anti-arrhythmic medications, amiodarone and d,l sotalol, around the HCN4 channel current was analyzed in HEK293 cells. Amiodarone potently inhibited the HCN4 channel current. The IC50 value of amiodarone for inhibiting of the HCN4 channel current at 70 mV was 4. 5 uM, which was very near to the therapeutic focus. In comparison, d,l sotalol at 1 300 uM scarcely inhibited the HCN4 channel current at 70 mV, even though drug slightly inhibited the current at hyperpolarizing voltages below 100 mV. Thus, the value of d,l sotalol for suppressing the HCN4 channel current at 70 mV couldn’t be determined. On the HCN4 channel current in HEK293 cells, we examined results of the class IV antiarrhythmic drugs, bepridil and verapamil.

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