Effect of agmatine on L-type calcium current in rat ventricular myocytes

Abstract

Aim: To study the effect of agmatine (Agm) on L-type calcium current (I(Ca-L)) in rat ventricular myocytes.

Methods: Whole-cell configuration of the patch-clamp technique was used to record I(Ca-L) in single rat ventricular myocytes which were dissociated by enzymatic dissociation method.

Results: (1) Agm (0.5, 1, 2 mmol/L) reduced the voltage-dependently activated peak amplitude of I(Ca-L) (pA) from 1451+/-236 (control) to 937+/-105 (n=8, P <0.05), 585+/-74 (n=8, P <0.01), and to 301+/-156 (n=8, P <0.01) in a concentration-dependent manner. (2) Agm (1 mmol/L) blocked I(Ca-L) in a use-dependent manner. The degree of use-dependent blocking effect was 53 %+/-12 % (n=8, P <0.05) at 1 Hz, and 69 %+/-11 % (n=8, P <0.01) at 3 Hz. (3) Agm upshifted the current-voltage (I-V) curve, but the characteristics of I-V relationship were not significantly altered by Agm, the maximal activation voltage of I(Ca-L) was not different from that of control. Steady-state activation of I(Ca-L) was not affected markedly. The half activation potential (V(0.5)) and the slope factor (k) were not significantly different from those of the control. V(0.5) value was (-20.2+/-2.5) mV in the control and (-20.5+/-2.7) mV in the presence of Agm 1 mmol/L. The k value was (7.1+/-0.4) mV and (7.5+/-0.5) mV, respectively (n=8, P >0.05). (4) Agm 1 mmol/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 (-32+/-6) mV in the control and (-40+/-5) mV in the presence of Agm. The k value was (7.6+/-0.9) mV and (12.5+/-1.1) mV, respectively (n=8, P <0.05). (5) Agm 1 mmol/L markedly delayed half-recovery time of Ca2+ channel from inactivation (92+/-28) ms to (249+/-26) ms (n=8, P <0.01).

Conclusion: Agm inhibited I(Ca-L) and mainly acted on the inactivated state of L-type calcium channel, manifested as acceleration of calcium channel inactivation and slowdown of recovery from inactivated state in rat ventricular myocytes.