AIM:To explore if
dofetilide derivative CPU 228(V 03 ) possesses blockade effect on the L-type calcium channel in Guinea
Pig myocard ium. METHOD:The effect of CPU 228 on L-type calcium current (
I Ca.L) was investigated by convention whole-cell patch-clamping technique on
ventricular myocytes isolated from Guinea Pig.RESULT:CPU 228 inhibited I Ca.L in concentration-dependent manner with an IC 50 of 0.93 μmol/L. CPU 228,in the concentration range from 0.33 μmol/L to 3.3 μmol/L,caused the I Ca.L I-V curve upward without alter ing the shape of the I-V curve and no significant changes to the steady-state activation curve of I Ca.L including V 1/2 and k were observe d. CPU 228 in the range from 0.33～3.3 μmol/L,markedly shifted the steady-s tate inactivation curve towards more negative potential in concentration-depend ent manner,and increased the V 1/2 from -(21.5±2.3)mV to -(40.0±4. 3)mV, but did not alter the slope factor(k).CONCLUSION:By chemical modification to dofetilide,CPU 228 possesses an effective blockade o n the L-type calcium channels in Guinea Pig ventricular myocytes via the su gges ted mechanism of inactivation. Antiarrhythmic action of CPU 228 is stronger than that of dofetilide while CPU 228 shows weaker action leading to arrhvthmia than the latter does.