G-protein- and cAMP-dependent L-channel gating modulation:: a manyfold system to control calcium entry in neurosecretory cells
G-protein- and cAMP-dependent L-channel gating modulation:: a manyfold system to control calcium entry in neurosecretory cells
复制标题
DOI：
10.1007/s004240100607
复制
发表时间：
2001-09-01
影响因子：
4.5
通讯作者：
Giusta, L
中科院分区：
文献类型：
--
作者：
Carbone, E;Carabelli, V;Giusta, L
电压门控性钙通道对神经分泌细胞中钙离子内流的控制至关重要。在肾上腺髓质的嗜铬细胞中，旁分泌或自分泌释放的神经递质诱导Ca 2+通道门控和控制儿茶酚胺分泌和细胞活性的Ca 2+依赖性事件的深刻变化。这些过程的普遍观点是，神经递质诱导的调节最广泛表达的Ca 2+通道在这些细胞（N-，P/Q-和L-型）遵循两个不同的途径：一个直接的膜界定G（i/o）-蛋白诱导的抑制N-和P/Q-型和远程cAMP介导的L-通道的便利。这两种作用都依赖于电压，尽管在分子和动力学方面有显著不同。然而，最近的研究结果对这种简单的方案提出了挑战，并表明L通道不需要强的前脉冲来招募或促进。它们在正常去极化期间可用，并且可以被释放的神经递质激活的G（i/o）蛋白质紧张性抑制。与N-和P/Q-通道一样，这种自分泌调节定位于膜微区。然而，与N-和P/Q-通道不同，L-通道的抑制在很大程度上不依赖于电压，并且与cAMP介导的通道门控增强平行发展。由于L-通道在嗜铬细胞释放儿茶酚胺的调控中起着至关重要的作用，G（i/o）蛋白和cAMP介导的两种相反的调节可能是扩大Ca 2+信号控制胞吐的动态范围的有效途径。在这里，我们回顾了这种新的L-型通道抑制的基本特征，将其与已建立的L-通道增强和电压依赖性易化形式进行比较。
Voltage-gated Ca2+ channels are crucial to the control of Ca2+ entry in neurosecretory cells. In the chromaffin cells of adrenal medulla, paracrinally or autocrinally released neurotransmitters induce profound changes in Ca2+ channel gating and Ca2+-dependent events controlling catecholamine secretion and cell activity. The generally held view of these processes is that neurotransmitter-induced modulation of the most widely expressed Ca2+ channels in these cells (N-, P/Q- and L-type) follows two distinct pathways: a direct membrane-delimited G(i/o)-protein-induced inhibition of N- and P/Q-type and a remote cAMP-mediated facilitation of L-channels. Both actions depend on voltage, although with remarkably different molecular and kinetic aspects. Recent findings, however, challenge this simple scheme and suggest that L-channels do not require strong pre-pulses to be recruited or facilitated. They are available during normal depolarizations and may be tonically inhibited by G(i/o) proteins activated by the released neurotransmitters. Like the N- and P/Q-channels, this autocrine modulation is localized to membrane microareas. Unlike N- and P/Q-channels, however, the inhibition of L-channels is largely independent of voltage and develops in parallel with cAMP-mediated potentiation of channel gating. As L-channels play a crucial role in the control of catecholamine release in chromaffin cells, the two opposite modulations mediated by G(i/o) proteins and cAMP may represent an effective way to broaden the dynamic range of Ca2+ signals controlling exocytosis. Here, we review the basic features of this novel L-type channel inhibition comparing it to the well-established forms of L-channel potentiation and voltage-dependent facilitation.