Voltage-gated channels and calcium homeostasis in mammalian rod photoreceptors
Voltage-gated channels and calcium homeostasis in mammalian rod photoreceptors
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DOI：
10.1152/jn.00874.2004
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发表时间：
2005-03-01
影响因子：
2.5
通讯作者：
Picaud, S
中科院分区：
文献类型：
--
作者：
Cia, D;Bordais, A;Picaud, S
最近关于 Ca2+ 通道阻滞剂对视杆细胞感光神经保护作用的报道指出，需要评估这些阻滞剂对哺乳动物视杆细胞的影响。然而，在哺乳动物中，视杆电生理学特征由于这些光感受器的小尺寸而受到阻碍，相反，这些光感受器在非哺乳动物脊椎动物中得到了广泛的研究。为了进一步表征离子电导并评估哺乳动物视杆细胞中 Ca2+ 通道的药理学，用全细胞膜片钳技术记录了新鲜分离的猪视杆细胞光感受器。杆细胞表达 1) 对外部 Cs+ 敏感的超极化激活的内向整流电导 (I-h)； 2) 对四乙铵敏感的持续外向 K+ 电流 (I-K) 3) 对苯并硫氮卓 (地尔硫卓) 和苯烷基胺 (维拉帕米) 衍生物敏感的持续电压门控 Ca2+ 电流 (I-Ca) 4) Ca2+ 激活的 Cl- 电流 (I-Cl(Ca)；5) 质膜 Ca2+-ATP 酶。 Ca 21 电流显示出从正电势到-60mV的激活范围，最大值在-30和-20mV之间。与其他 L 型 Ca2+ 通道相反，杆状 Ca2+ 通道在相似且相对较高的浓度下被地尔硫卓异构体和维拉帕米阻断。 D-地尔硫卓的双相剂量反应证实了 Ca2+ 通道对该分子的低敏感性。位于轴突末端的 ATP 酶被发现有助于 Ca2+ 的排出。这些结果表明，杆状光感受器的电生理特征在从非哺乳动物脊椎动物到哺乳动物的进化过程中得到了保留。这项工作进一步表明，哺乳动物视杆细胞表达非经典的 L 型 Ca2+ 通道，对神经保护研究中使用的地尔硫卓异构体表现出较低的敏感性。
Recent reports on rod photoreceptor neuroprotection by Ca2+ channel blockers have pointed out the need to assess the effect of these blockers on mammalian rods. However, in mammals, rod electrophysiological characterization has been hampered by the small size of these photoreceptors, which were instead extensively studied in nonmammalian vertebrates. To further characterize ionic conductances and to assess the pharmacology of Ca2+ channels in mammalian rods, freshly dissociated pig rod photoreceptors were recorded with the whole cell patch-clamp technique. Rod cells expressed 1) a hyperpolarization-activated inward-rectifying conductance (I-h) sensitive to external Cs+; 2) a sustained Outward K+ current (I-K) sensitive to tetraethylammonium 3) a sustained voltage-gated Ca2+ current (I-Ca) sensitive to benzothiazepine (diltiazem) and phenylalkylamine (verapamil) derivatives 4) a Ca2+-activated Cl- current (I-Cl(Ca); and 5) a plasma membrane Ca2+-ATPase. The Ca 21 current showed a range of activation from positive potentials to -60 mV with a maximum between -30 and -20 mV. In contrast to other L-type Ca2+ channels, rod Ca2+ channels were blocked at similar and relatively high concentrations by the diltiazem isomers and verapamil. The biphasic dose-response for D-diltiazem confirmed the low sensitivity of Ca2+ channels for the molecule. The ATPase, which was localized at the axon terminal, was found to contribute to Ca2+ extrusion. These results suggest that the electrophysiological features of rod photoreceptors had been preserved during evolution from nonmammalian vertebrates to mammals. This work indicates further that mammalian rods express nonclassic L-type Ca2+ channels, showing a low sensitivity to the diltiazem isomers used in neuroprotective studies.