Akopian A, Johnson J, Gabriel R, Brecha N, Witkovsky P
Department of Ophthalmology, New York University School of Medicine, New York, New York 10016, USA.
J Neurosci. 2000 Feb 1;20(3):929-36. doi: 10.1523/JNEUROSCI.20-03-00929.2000.
We investigated the cellular localization in the salamander retina of one of the somatostatin [or somatotropin release-inhibiting factor (SRIF)] receptors, sst(2A), and studied the modulatory action of SRIF on voltage-gated K(+) and Ca(2+) currents in rod and cone photoreceptors. SRIF immunostaining was observed in widely spaced amacrine cells, whose perikarya are at the border of the inner nuclear layer and inner plexiform layer. sst(2A) immunostaining was seen in the inner segments and terminals of rod and cone photoreceptors. Additional sst(2A) immunoreactivity was expressed by presumed bipolar and amacrine cells. SRIF, at concentrations of 100-500 nM, enhanced a delayed outwardly rectifying K(+) current (I(K)) in both rod and cone photoreceptors. SRIF action was blocked in cells pretreated with pertussis toxin (PTX) and was substantially reduced by intracellular GDP(beta)S. Voltage-gated L-type Ca(2+) currents in rods and cones were differently modulated by SRIF. SRIF reduced Ca(2+) current in rods by 33% but increased it in cones by 40%, on average. Both effects were mediated via G-protein activation and blocked by PTX. Ca(2+)-imaging experiments supported these results by showing that 500 nM SRIF reduced a K(+)-induced increase in intracellular Ca(2+) in rod photoreceptor terminals but increased it in those of cones. Our results suggest that SRIF may play a role in the regulation of glutamate transmitter release from photoreceptors via modulation of voltage-gated K(+) and Ca(2+) currents.
我们研究了生长抑素[或生长激素释放抑制因子(SRIF)]受体之一sst(2A)在蝾螈视网膜中的细胞定位,并研究了SRIF对视杆和视锥光感受器中电压门控K(+)和Ca(2+)电流的调节作用。在间隔较宽的无长突细胞中观察到SRIF免疫染色,这些细胞的胞体位于内核层和内网状层的边界。在视杆和视锥光感受器的内段和终末可见sst(2A)免疫染色。推测的双极细胞和无长突细胞也表达额外的sst(2A)免疫反应性。浓度为100 - 500 nM的SRIF增强了视杆和视锥光感受器中的延迟外向整流K(+)电流(I(K))。SRIF的作用在用百日咳毒素(PTX)预处理的细胞中被阻断,并且被细胞内GDP(β)S显著降低。视杆和视锥中的电压门控L型Ca(2+)电流受到SRIF的不同调节。平均而言,SRIF使视杆中的Ca(2+)电流降低33%,但使视锥中的Ca(2+)电流增加40%。这两种效应均通过G蛋白激活介导,并被PTX阻断。Ca(2+)成像实验支持了这些结果,表明500 nM的SRIF降低了视杆光感受器终末中K(+)诱导的细胞内Ca(2+)增加,但增加了视锥光感受器终末中的这种增加。我们的结果表明,SRIF可能通过调节电压门控K(+)和Ca(2+)电流,在调节光感受器释放谷氨酸递质中发挥作用。