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犬支气管肌细胞延迟整流钾电流:花粉致敏和蛋白激酶C激活的影响

Delayed rectifier K+ current of dog bronchial myocytes: effect of pollen sensitization and PKC activation.

作者信息

Waldron G J, Sigurdsson S B, Aiello E A, Halayko A J, Stephens N L, Cole W C

机构信息

Smooth Muscle Research Group, Faculty of Medicine, University of Calgary, Calgary, Alberta T2N 4N1.

出版信息

Am J Physiol. 1998 Aug;275(2):L336-47. doi: 10.1152/ajplung.1998.275.2.L336.

Abstract

The properties of delayed rectifier K+ current [IK(dr)] of canine airway smooth muscle cells isolated from small bronchi and its modulation by protein kinase C (PKC) were studied by whole cell patch clamp. IK(dr) activated positive to -40 mV, with half-maximal activation at -16 +/- 1.2 mV (n = 15) and average current density of 31 +/- 2.6 pA/pF (n = 15) at +30 mV. The capacitive surface area, current density, and voltage dependence of activation of IK(dr) of myocytes of ragweed pollen-sensitized dogs were not different from age-matched control dogs. However, the sensitization reduced the availability of IK(dr) between -40 and -20 mV due to a hyperpolarizing shift in the voltage dependence of steady-state inactivation (-29.9 +/- 1.2 in sensitized versus -26.0 +/- 0.7 mV in control dogs, n = 9 and 11, respectively; P < 0.05). PKC activation with diacylglycerol analog or phorbol ester depressed IK(dr) amplitude, whereas an inactive diacylglycerol analog had no effect. The hyperpolarizing shift in voltage dependence of inactivation and/or modulation of IK(dr) by PKC may be two mechanisms that contribute to the enhanced reactivity of bronchial tissues from ragweed pollen-sensitized dogs.

摘要

采用全细胞膜片钳技术研究了从小支气管分离的犬气道平滑肌细胞延迟整流钾电流[IK(dr)]的特性及其蛋白激酶C(PKC)的调节作用。IK(dr)在-40 mV时开始激活,半最大激活电压为-16±1.2 mV(n = 15),在+30 mV时平均电流密度为31±2.6 pA/pF(n = 15)。豚草花粉致敏犬的心肌细胞IK(dr)的电容表面积、电流密度和激活电压依赖性与年龄匹配的对照犬无差异。然而,由于稳态失活电压依赖性的超极化偏移,致敏作用降低了IK(dr)在-40至-20 mV之间的可用性(致敏犬为-29.9±1.2,对照犬为-26.0±0.7 mV,n分别为9和11;P<0.05)。用二酰基甘油类似物或佛波酯激活PKC可降低IK(dr)幅度,而无活性的二酰基甘油类似物则无作用。PKC引起的失活电压依赖性超极化偏移和/或IK(dr)调节可能是导致豚草花粉致敏犬支气管组织反应性增强的两种机制。

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