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多巴胺以不同方式调节鲈鱼视网膜水平细胞中的T型和L型钙电流。

Dopamine modulates in a differential fashion T- and L-type calcium currents in bass retinal horizontal cells.

作者信息

Pfeiffer-Linn C, Lasater E M

机构信息

Department of Ophthalmology, University of Utah, School of Medicine, Salt Lake City 84108.

出版信息

J Gen Physiol. 1993 Aug;102(2):277-94. doi: 10.1085/jgp.102.2.277.

Abstract

White bass (Roccus chrysops) retinal horizontal cells possess two types of voltage-activated calcium currents which have recently been characterized with regard to their voltage dependence and pharmacology (Sullivan, J., and E. M. Lasater. 1992. Journal of General Physiology. 99:85-107). A low voltage-activated transient current was identified which resembles the T-type calcium current described in a number of other preparations, along with a sustained high threshold, long-lasting calcium current that resembles the L-type calcium current. Here we report on the modulation of horizontal cell calcium channels by dopamine. Under whole-cell voltage clamp conditions favoring the expression of both calcium currents, dopamine had opposing actions on the two types of voltage-sensitive calcium currents in the same cone-type horizontal cell. The L-type calcium current was significantly potentiated by dopamine while the T-type current was simultaneously reduced. Dopamine had no effect on calcium currents in rod-type horizontal cells. Both of dopamine's actions were mimicked with the D1 receptor agonist, SKF 38393, and blocked by application of the D1 specific antagonist, SCH 23390. Dopamine's actions on the two types of calcium currents in white bass horizontal cells are mimicked by the cell membrane-permeant cyclic AMP derivative, 8-(4-chlorophenylthio)-cyclic AMP, suggesting that dopamine's action is linked to a cAMP-mediated second messenger system. Furthermore, the inhibitor of cAMP-dependent protein kinase blocked both of dopamine's actions on the voltage-dependent calcium channels when introduced through the patch pipette. This indicates that protein phosphorylation is involved in modulating horizontal cell calcium channels by dopamine. Taken together, these results show that dopamine has differential effects on the voltage-dependent calcium currents in retinal horizontal cells. The modulation of these currents may play a role in shaping the response properties of horizontal cells.

摘要

白鲈(Roccus chrysops)视网膜水平细胞具有两种电压激活钙电流,最近已对其电压依赖性和药理学特性进行了表征(沙利文,J.,和E.M.拉萨特。1992年。《普通生理学杂志》。99:85 - 107)。已鉴定出一种低电压激活的瞬态电流,它类似于在许多其他标本中描述的T型钙电流,同时还有一种持续的高阈值、持久的钙电流,类似于L型钙电流。在此,我们报告多巴胺对水平细胞钙通道的调节作用。在有利于两种钙电流表达的全细胞电压钳制条件下,多巴胺对同一锥体型水平细胞中的两种电压敏感钙电流具有相反的作用。多巴胺显著增强L型钙电流,同时降低T型电流。多巴胺对杆体型水平细胞的钙电流没有影响。多巴胺的这两种作用都被D1受体激动剂SKF 38393模拟,并被应用D1特异性拮抗剂SCH 23390阻断。细胞膜可渗透的环磷酸腺苷衍生物8 -(4 - 氯苯基硫代)-环磷酸腺苷模拟了多巴胺对白鲈水平细胞中两种钙电流的作用,这表明多巴胺的作用与环磷酸腺苷介导的第二信使系统有关。此外,当通过膜片吸管引入时,环磷酸腺苷依赖性蛋白激酶抑制剂阻断了多巴胺对电压依赖性钙通道的两种作用。这表明蛋白磷酸化参与了多巴胺对水平细胞钙通道的调节。综上所述,这些结果表明多巴胺对视网膜水平细胞中的电压依赖性钙电流具有不同的影响。这些电流的调节可能在塑造水平细胞的反应特性中起作用。

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