OBJECTIVE To investigate the effects of cryptotanshinone(CTS) on experimental atrial fibrillation(AF) in SD rats and explore its possible ion channel mechanisms.

METHODS  Intravenous injection of calcium chloride-acetylcholine was used to induce AF in SD rats in vivo. Single rat atrial myocytes were isolated by Langendorff retrograde perfusion and three-step gradient calcium extraction method that met the experimental requirements. Whole-cell patch-clamp technique was used to observe, record, and analyze the effects of 15, 30, and 60 μmol·L⁻¹ CTS on the transient outward potassium current(I_to) of rat atrial myocytes.

RESULTS The result of in vivo experiments indicated that compared with the model control group, the CTS preventive administration at doses of 5, 10, and 20 mg·kg⁻¹ gradually prolonged the time of AF induction in the experimental animals, while the duration of AF decreased gradually(P<0.01), and the incidence of AF had no significant influence. The results of the patch-clamp experiments showed that 15, 30, and 60 μmol·L⁻¹ CTS gradually reduced the peak value of I_to, showing a concentration-dependent inhibition(P<0.01). In terms of channel kinetics, 15, 30, and 60 μmo·L⁻¹ CTS significantly shifted the I_to current-voltage relationship curve downward; the steady-state activation curve showed no significant change; the steady-state inactivation curves were sequentially shifted to the left in each concentration, with the half-inactivation voltage(V_1/2-inactive) gradually decreasing(P<0.01); the inactivation recovery curve was shifted to the right, with the recovery time constant(τ) gradually increasing(P<0.01). These results indicated that CTS could inhibit the occurrence of AF in the model animals, suppress I_to, and regulate the dynamic processes of I_to inactivation and recovery.

CONCLUSION  CTS has an anti-calcium-acetylcholine induced AF effect in rats, and the occurrence of this effect may be related to the inhibition of I_to and alteration of its kinetic course by the drug.