Mears David
Department of Anatomy, Physiology and Genetics, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, Maryland 20814, USA.
J Membr Biol. 2004 Jul 15;200(2):57-66. doi: 10.1007/s00232-004-0692-9.
Insulin secretion from beta-cells of the pancreatic islets of Langerhans is triggered by Ca(2+) influx through voltage-dependent Ca(2+) channels. Electrophysiological and molecular studies indicate that beta-cells express several subtypes of these channels. This review discusses their roles in regulating insulin secretion, focusing on recent studies using beta-cells, exogenous expression systems, and Ca(2+) channel knockout mice. These investigations reveal that L-type Ca(2+) channels in the beta-cell physically interact with the secretory apparatus by binding to synaptic proteins on the plasma membrane and insulin granule. As a result, Ca(2+) influx through L-type channels efficiently and rapidly stimulates release of a pool of insulin granules in close contact with the channels. Thus, L-type Ca(2+) channel activity is preferentially coupled to exocytosis in the beta-cell, and plays a critical role in regulating the dynamics of insulin secretion. Non-L-type channels carry a significant portion of the total voltage-dependent Ca(2+) current in beta-cells and cell lines from some species, but nevertheless account for only a small fraction of insulin secretion. These channels may regulate exocytosis indirectly by affecting membrane potential or second messenger signaling pathways. Finally, voltage-independent Ca(2+) entry pathways and their potential roles in beta-cell function are discussed. The emerging picture is that Ca(2+) channels regulate insulin secretion at multiple sites in the stimulus-secretion coupling pathway, with the specific role of each channel determined by its biophysical and structural properties.
朗格汉斯胰岛β细胞的胰岛素分泌是由通过电压依赖性Ca(2+)通道的Ca(2+)内流触发的。电生理学和分子研究表明，β细胞表达这些通道的几种亚型。本综述讨论了它们在调节胰岛素分泌中的作用，重点是最近使用β细胞、外源表达系统和Ca(2+)通道敲除小鼠的研究。这些研究表明，β细胞中的L型Ca(2+)通道通过与质膜和胰岛素颗粒上的突触蛋白结合，与分泌装置发生物理相互作用。因此，通过L型通道的Ca(2+)内流有效且迅速地刺激了与通道紧密接触的一群胰岛素颗粒的释放。因此，L型Ca(2+)通道活性优先与β细胞中的胞吐作用偶联，并在调节胰岛素分泌的动力学中起关键作用。非L型通道在某些物种的β细胞和细胞系中携带了总电压依赖性Ca(2+)电流的很大一部分，但在胰岛素分泌中仅占一小部分。这些通道可能通过影响膜电位或第二信使信号通路间接调节胞吐作用。最后，讨论了电压依赖性Ca(2+)进入途径及其在β细胞功能中的潜在作用。新出现的情况是，Ca(2+)通道在刺激-分泌偶联途径的多个位点调节胰岛素分泌，每个通道的具体作用由其生物物理和结构特性决定。
