内皮素对慢性低氧大鼠肺动脉平滑肌细胞膜钾通道活性的影响

目的观察内皮素(ET-1)对慢性低氧大鼠肺动脉平滑肌细胞(PASMCs)膜电压门控钾通道(K_V)活性的影响。方法将12只Wistar大鼠随机分为对照组和慢性低氧组，每组6只。用全细胞膜片钳记录方法研究ET-1对两组大鼠PASMCs膜电位(E_m)、膜电容(C_m)及电压门控钾电流(IK_V)的影响。结果ET-1可引起两组大鼠PASMCs去极化，且对两组大鼠IK_V均有明显的浓度依赖性抑制作用。在慢性低氧组，高浓度ET-1对IK_V的抑制作用强于对照组。结论低氧并未改变ET-1引起PASMCs去极化及浓度依赖性抑制IK_V的特性，且慢性低氧可能改变了PASMCs对ET-1的敏感性，内皮素和低氧对PASMCs IK_V的抑制作用有协同性。

Effect of endothelin-1 on voltage-gated K+ current in the pulmonary artery smooth muscle cells of chronic hypoxic rats

AIM: To investigate the effect of endothelin-1 (ET-1) on voltage-gated K+ current in the pulmonary artery smooth muscle cells (PASMCs) of chronic hypoxic rats. METHODS: Twelve male Wistar rats matched with age and body weight were randomly divided into control and chronic hypoxic groups. Single PASMCs were obtained with acute enzyme (collagnase plus papain) dispersing method. Using the whole cell patch clamp technique in freshly isolated PASMCs from normoxic and hypoxic rats, the effects of ET-1 on voltage-gated K+ current were recorded. RESULTS: The resting membrane potential (Em) in PASMCs from chronic hypoxic rats was significantly depolarized to (-32.6 +/- 1.3) mV compared with (-42.1 +/- 2.8) mV in PASMCs from normoxic rats (P < 0.01, n = 20). In chronic hypoxic rats, the IKv was smaller than that in normotensive rats +50 mV, the peak current density of control group reduced from (136 +/- 24) pA/pF to (98 +/- 12) pA/pF, percent inhibition was (28.4 +/- 2.4)%, P < 0.01, n = 6]. Application of ET-1 (1 x 10(-8) mol x L(-1)) also depolarized PASMCs of chronic hypoxic rats from (-32.6 +/- 1.3) mV to (-21.5 +/- 1.7) mV (P < 0.05, n = 20) compared with the ET-1 induced depolarization from (-42.1 +/- 2.8) mV to (-22.6 +/- 1.4) mV (P < 0.05, n = 20). The change in membrane potential induced by ET-1 was not significantly different between PASMCs from normoxic and hypoxic rats. ET-1 (1 x 10(-10) to 1 x 10(-7) mol x L(-1)) caused concentration-dependent inhibition of K+ current in PASMCs both from normoxic and hypoxic rats. At higher concentration (1 x 10(-8) - 1 x 10(-7) mol x L(-1)), the effect of ET-1 on K+ current in PASMCs from hypoxic rats was greater than that of normoxic rats +50 mV, the peak current density of control group reduced from (136 +/- 24) pA/pF to (40 +/- 10) pA/pF, percent inhibition was (71 +/- 7)%, that of hypoxic group was (98 +/- 6) pA/pF to (16 +/- 3) pA/pF, percent inhibition was (85 +/- 10)% at 1 x 10(-7) mol x L(-2), n = 6, P < 0.01]. CONCLUSION: Chronic hypoxia did not change the effect of ET-1 on the passive electrical properties of PASMCs. In both normotensive and chronic hypoxic hypertensive PASMCs, exogenous ET-1 could cause concentration-dependent inhibition of voltage-gated K+ current, and the inhibition of K+ current in PASMCs from chronic hypoxic rats was greater than that from normoxic rats at higher concentration (1 x 10(-8) - 1 x 10(-7) mol x L(-1)). Chronic hypoxia might alter the sensitivity of PASMCs to ET-1, perhaps PASMCs exposed to chronic hypoxia were more susceptible to ET-1 mediated IKv inhibition.