Effect of dipfluzine on L-type calcium current in guinea pig ventricular myocytes
Abstract
Aim: To study the effect of dipfluzine (Dip) on L-type calcium current in guinea pig ventricular myocytes.
Methods: Single myocytes were dissociated by enzymatic dissociation method. The current was recorded with the whole-cell configuration of the patch-clamp technique.
Results: Dip (0.3 - 30 micromol/L) reduced the voltage-dependently activated peak value of I(Ca-L) in a concentration-dependent manner. The characteristics of I-V relationship were not greatly altered by Dip, and the maximal activation voltage of I(Ca-L) in the presence of Dip was not different from that of control. Steady-state activation of I(Ca-L) was not affected markedly, and the half activation potential V(0.5)) and the slope factor (kappa) in the presence of Dip 3 micromol/L were not markedly different from those of the control. V(0.5) value was (-12.8 +/- 1.7) mV in the control and (-13.2 +/- 2.4) mV in the presence of Dip 3 micromol/L. The kappa value was (7.1 +/- 0.4) mV in the control and (7.5 +/- 0.5) mV in the presence of Dip 3 micromol/L (n = 7 cells from 3 hearts, P > 0.05). Dip 3 micromol/L markedly shifted the steady-state inactivation curve of I(Ca-L) to the left, and accelerated the voltage-dependent steady-state inactivation of calcium current. V(0.5) value was (-19.7 +/- 2.4) mV in the control and (-31 +/- 6) mV in the presence of Dip 3 micromol/L. The kappa value was (3.6 +/- 0.3) mV in the control and (1.8 +/- 0.2) mV in the presence of Dip 3 micromol/L (n = 4 cells from 2 hearts, P < 0.05). Dip 3 micromol/L markedly delayed half-recovery time of Ca2+ channel from inactivation from (40 +/- 11) to (288 +/- 63) ms (n = 4, P < 0.01).
Conclusion: Dip mainly acts on the inactivated state of L-type calcium channel, accelerates the inactivation of calcium channel, and slows the recovery of calcium channel from inactivated state in guinea pig ventricular myocytes, through which the I(Ca-L) is inhibited.
Keywords:
Methods: Single myocytes were dissociated by enzymatic dissociation method. The current was recorded with the whole-cell configuration of the patch-clamp technique.
Results: Dip (0.3 - 30 micromol/L) reduced the voltage-dependently activated peak value of I(Ca-L) in a concentration-dependent manner. The characteristics of I-V relationship were not greatly altered by Dip, and the maximal activation voltage of I(Ca-L) in the presence of Dip was not different from that of control. Steady-state activation of I(Ca-L) was not affected markedly, and the half activation potential V(0.5)) and the slope factor (kappa) in the presence of Dip 3 micromol/L were not markedly different from those of the control. V(0.5) value was (-12.8 +/- 1.7) mV in the control and (-13.2 +/- 2.4) mV in the presence of Dip 3 micromol/L. The kappa value was (7.1 +/- 0.4) mV in the control and (7.5 +/- 0.5) mV in the presence of Dip 3 micromol/L (n = 7 cells from 3 hearts, P > 0.05). Dip 3 micromol/L markedly shifted the steady-state inactivation curve of I(Ca-L) to the left, and accelerated the voltage-dependent steady-state inactivation of calcium current. V(0.5) value was (-19.7 +/- 2.4) mV in the control and (-31 +/- 6) mV in the presence of Dip 3 micromol/L. The kappa value was (3.6 +/- 0.3) mV in the control and (1.8 +/- 0.2) mV in the presence of Dip 3 micromol/L (n = 4 cells from 2 hearts, P < 0.05). Dip 3 micromol/L markedly delayed half-recovery time of Ca2+ channel from inactivation from (40 +/- 11) to (288 +/- 63) ms (n = 4, P < 0.01).
Conclusion: Dip mainly acts on the inactivated state of L-type calcium channel, accelerates the inactivation of calcium channel, and slows the recovery of calcium channel from inactivated state in guinea pig ventricular myocytes, through which the I(Ca-L) is inhibited.