Protoporphyrins modulate voltage-gated Ca current in AtT-20 pituitary cells.
Protoporphyrins modulate voltage-gated Ca current in AtT-20 pituitary cells.
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原卟啉调节 AtT-20 垂体细胞中的电压门控 Ca 电流。
DOI：
10.1152/jn.1993.70.6.2673
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发表时间：
1993
影响因子：
2.5
通讯作者：
Gurfel,D
中科院分区：
文献类型：
--
作者：
Linden,DJ;Narasimhan,K;Gurfel,D
1.锌-原卟啉-IX（ZnPP-IX）是血红素加氧酶-2（HO-2）的抑制剂，因此已被用于检查神经组织中一氧化碳产生的作用。我们已经测量了电压门控钙电流AtT-20垂体细胞使用全细胞膜片钳技术，并评估了细胞外应用ZnPP-IX和相关化合物的影响。2.在-90 mV的保持电位下，由去极化步骤诱发的钙电流为高阈值、缓慢失活型。该电流的五十六%被10 μ M硝苯地平阻断，16%被3 μ M ω-芋螺毒素阻断，其余对两种药物的组合具有抗性，这表明总Ca电流是L、N和可能的P型电导的混合物。3.浴应用ZnPP-IX导致不可逆的，剂量依赖性衰减的钙电流。5微摩尔ZnPP-IX产生了62%的峰值电流幅度的减少，在电流-电压关系中没有偏移，0.5微摩尔产生了19%的减少，和0.05微摩尔产生了可变的响应，无论是小的瞬态衰减或增强。4. 5 μ M ZnPP-IX对Ca电流的衰减几乎可以被浴中超氧化物歧化酶（90 U/ml）的共同应用完全阻断，但不能被向内部盐水（KT 5823，1 μ M）中加入cGMP依赖性蛋白激酶的抑制剂所阻断。5.具有类似效力的血红素加氧酶的其他抑制剂，如锡-原卟啉-IX（Sn-PP-IX）和锌-次卟啉-双-乙二醇（ZnBG），当以5 μ M施加时不减弱Ca电流。（400字处截断摘要）
1. Zinc-protoporphyrin-IX (ZnPP-IX) is an inhibitor of the enzyme heme-oxygenase-2 (HO-2) and consequently has been used to examine the role of carbon monoxide production in neural tissues. We have measured voltage-gated Ca current in AtT-20 pituitary cells using the whole-cell patch-clamp technique and have assessed the effects of extracellularly applied ZnPP-IX and related compounds. 2. Ca currents evoked by depolarizing steps from a holding potential of -90 mV were of the high-threshold, slowly inactivating type. Fifty-six percent of this current was blocked by 10 microM nifedipine and 16% by 3 microM omega-conotoxin with the remainder resistant to both drugs in combination, suggesting that the total Ca current was a mixture of L, N, and possibly P-type conductances. 3. Bath application of ZnPP-IX resulted in an irreversible, dose-dependent attenuation of Ca current. Five micromolar ZnPP-IX produced a 62% reduction of peak current amplitude with no shift in the current-voltage relation, 0.5 microM produced a 19% reduction, and 0.05 microM produced a variable response, either a small transient attenuation or potentiation. 4. The attenuation of Ca current by 5 microM ZnPP-IX could be nearly completely blocked by co-application of superoxide dismutase in the bath (90 U/ml) but not by addition of an inhibitor of cGMP-dependent protein kinase to the internal saline (KT5823, 1 microM). 5. Other inhibitors of heme-oxygenase with similar potency such as tin-protoporphyrin-IX (Sn-PP-IX) and Zn-deuteroporphyrin-bis-glycol (ZnBG) did not attenuate Ca current when applied at 5microM.(ABSTRACT TRUNCATED AT 400 WORDS)