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目的观察氯胺酮对豚鼠心室肌细胞膜L-型钙电流(ICa-L)的影响。方法酶解法分离单个心室肌细胞,采用全细胞膜片钳技术,观察100μmol/L氯胺酮在不同钳制电压下以及不同浓度 (50-5 000μmol/L)氯胺酮在+10mV钳制电压下豚鼠心室肌细胞膜ICa-L的变化,并研究100μmol/L氯胺酮对ICa-L稳态激活曲线、稳态失活曲线和稳态失活后恢复曲线的影响。结果 100μmol/L氯胺酮抑制ICa-L,使电流密度-电压曲线上移,但不改变激活电压、峰值电压、翻转电压以及曲线形态;细胞外液冲洗后,ICa-L部分恢复。保持电压-40 mV、钳制电压+10 mV条件下,100-5 000 μmol/L氯胺酮呈浓度依赖性抑制ICa-L,其半数抑制浓度为926．6 μmol/L。100μmol/L氯胺酮对ICa-L激活曲线没有明显影响, 给药前后半数激活电压分别为-2．9±0．6、(-1．4±1．1)mV(P>0．05),斜率因子(k)分别为7．4±0． 5、(8．0±0．3)mV(P>0．05);100μmol/l氯胺酮使ICa-L的稳态失活曲线明显左移,给药前后半数失活电压分别为-14．8±0．8、(-19．6±0．7)mV(P<0．05),k分别为6．2±0．4、(5．9±0．3)mV(P>0．05); 100μmol/l氯胺酮使ICa-L的稳态失活后恢复曲线明显下移。结论氯胺酮可通过作用于L-钙通道的失活态,浓度依赖性地抑制豚鼠心室肌细胞ICa-L,产生负性肌力作用。
Objective To investigate the effects of ketamine on L-type calcium current (ICa-L) in guinea pig ventricular myocytes. Methods Single ventricular myocytes were isolated by enzyme-digestion. Whole-cell patch-clamp technique was used to observe the effects of 100μmol / L ketamine at different clamping voltage and different concentrations of ketamine (50-5 000μmol / L) at +10 mV clamping voltage. L and study the effects of 100μmol / L ketamine on ICa-L steady-state activation curve, steady-state inactivation curve and recovery curve after steady-state inactivation. Results ICa-L was inhibited by 100 μmol / L ketamine, and the current density-voltage curve was shifted upward without changing the activation voltage, peak voltage, voltage and curve shape. ICa-L partially recovered after washing with extracellular fluid. With a holding voltage of -40 mV and a clamping voltage of +10 mV, 100-5 000 μmol / L ketamine inhibited ICa-L in a concentration-dependent manner with a half maximal inhibitory concentration of 926.6 μmol / L. 100μmol / L ketamine had no significant effect on the activation of ICa-L, and the half activation voltage before and after administration was -2.9 ± 0.6, (-1.4 ± 1.1) mV (P> 0.05) The slope factor (k) is 7.4 ± 0 respectively. 5, (8.0 ± 0.3) mV (P> 0.05). 100 μmol / L ketamine significantly shifted the steady state inactivation curve of ICa-L to the left. 8 ± 0.8 and -19.6 ± 0.7 mV respectively (P <0.05), k were 6.2 ± 0.4 and 5.9 ± 0.3 mV respectively (P> 0 .05). The recovery curve of ICa-L after 100μmol / l ketamine declines steadily. Conclusions Ketamine can inhibit the ICa-L of guinea pig ventricular myocytes in a concentration-dependent manner by inhibiting the inactivation of L-type calcium channel, producing negative inotropic effect.