H-89对大鼠心肌细胞膜电流的影响

目的评估蛋白激酶A(PKA)抑制剂H-89对大鼠心室肌细胞膜主要离子通道和转运体的影响。方法应用全细胞膜片钳技术观察H-89对胶原酶分解的成年SD大鼠心室肌细胞膜离子电流L-型钙电流(ICa-L)、电压门控钠电流(INa)、内向整流钾电流(IK1)、瞬时外向钾电流(Ito)和钠钙交换体电流(INa/Ca)的影响。结果1～10μmol.L-1H-89可浓度依赖性抑制ICa-L、INa、Ito(P<0.05);对IK1有更强的抑制作用,在较低浓度(5μmol.L-1)时即可完全抑制IK1(P<0.05),与0.5mmol.L-1氯化钡的作用类似。但在1～10μmol.L-1浓度范围内H-89对INa/Ca无明显作用(P>0.05)。结论H-89对心肌细胞膜电流的影响可能是其对通道的直接作用或间接通过抑制PKA所致。

The effects of H-89 on membrane ion currents in rat ventricular myocytes

Aim To assess the effects of N -[2-p-bromo-cinnamylamino-ethyl]-5-isoquinoline-sulfonamide (H-89), a potentially selective inhibitor of Protein Kinase A (PKA), on cardiac membrane ion channels and transporters, which will further fulfill our understanding of pharmacology of PKA inhibitors.Methods Whole-cell patch clamp was used to investigate the effects of H-89 on cardiac L-type Ca~(2+) current (I_(Ca-L)), Na~+ current (I_(Na)), inward rectifier K~+ current (I_(K1)), transient outward K~+ current (I_(to)) and Na~+-Ca~2+ exchanger current (I_(Na/Ca)) in enzymatic dissociated SD rat ventricular myocytes.Results H-89 at 1～10 μmol·L~(-1) could inhibit I_(Ca-L) , I_(Na) , and Ito in a concentration-relative manner (P <0.05). At low concentra-tion (5 μmol·L~(-1)), H-89 completely inhibited I_(K1) (P <0.05) just as the action of 0.5 mmol·L~(-1) BaCl_2.Further, H-89 at 1～10 μmol·L~(-1) had no significant effect on I_(Na/Ca) (P >0.05).Conclusion The direct or PKA-mediated indirect action maybe involved in the effects of H-89 on ion currents and transporter.