Effect of ivabradine on hyperpolarization activated cation current in canine pulmonary vein sleeve cardiomyocytes with atrial fibrillation

Objective To study the effect of ivabradine on hyperpolarization activated cation current in canine pulmonary vein(PY) sleeve cardiomyocytes with atrial fibrillation. Methods Dissociation of PVs yielded single cardiomyocytes from a Landengorff column without or with pacemaker activity from long-term rapidly atrial pacing (RAP) canines. If current was measured with the whole-cell patch-clamp technique. Results Compared with the control group, the rapidly atrial pacing canine PV cardiomyocytes had spontaneous diastolic depolarization and had larger If densities. Ivabradine (Iva,1|ìM), a selective inhibitor of the If current, markedly reduced If currents in the RAP from -2.66±0.4 pA/pF to -1.58±0.1 pA/pF at the test potential of -120 mV (P<0.01,n=12). Inhibition effect of Iva of If current showed concentration-dependent range from 0.1 to 10.0 |ìM, with IC50 of 2.2 |ìM ( 1.8–2.9 |ìM, 95% CL). Furthermore, V1/2 of steady-state activated curve was shifted from -84.3±4.9 mV to -106.9±3.4 mV and k value of steady-state activated curve was changed from 12.1±2.6 mV to 9.9±3.4 mV by the application of. 1.0 |ìM Iva ( P<0.01, n=12). Conclusions Our study revealed that Ivarbadine may significantly decrease If of rapidly atrial pacing pulmonary vein sleeve cells with atrial fibrillation.