Whole-cell patch clamp measurements and berberine inhibition of hyperpolarization-activated inward current in rabbit...

Single rabbit sinoatrial node (SAN) cells were isolated by means of an enzymatic dispersion procedure and used for the whole-cell patch clamp experiment. At a holding potential of -40 mV, a time- and voltage-dependent inward current, I(f), was activated at different hyperpolarization potentials from -60 mV to -110 mV. The current-voltage relation curve showed that I(f) was activated at potential more negative than -40 mV. Five min after treatment by CsCl 2 mmol.L-1-containing Tyrode solution, I(f) was almost completely blocked. At a hyperpolarization potential of -110 mV, I(f) was reduced from 1.7 +/- 0.2 nA of the control to 1.2 +/- 0.4 nA after superfusing with Tyrode solution containing berberine (Ber) 1 mumol.L-1 for 5 min. And it was difficult to wash out this action. Ber also had inhibitory effects on other currents to a certain extent. The results indicate that I(f) is a Cs(+)-sensitive current and that the negative chronotropic effect of Ber may be due to the inhibition of I(f) that functions as an important pacemaking modulator for the spontaneous depolarization of SAN tissue.