ISLET CELL ELECTRICAL PACEMAKER MECHANISMS

胰岛细胞电起搏器机制

• 批准号: 3229058
• 负责人: DANIEL L COOK
• 金额: $ 15.42万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 1983
• 资助国家: 美国
• 起止时间: 1983-07-01 至 1991-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3229058
• 关键词: calcium metabolism; cell membrane; cyclic AMP; electronic stimulator; glucose; hormone regulation /control mechanism; insulin; ion transport; membrane permeability; pancreatic islet function

Glucose-induced membrane electrical activity of pancreatic B-cells mediates calcium uptake used for insulin release. The electrical response occurs in two glucose-dependent phases: as glucose level increases from zero to the threshold for insulin release, there is a subthreshold depolarization of the B-cell membrane. Additional glucose triggers both insulin release and electricalactivity. The electrical activity consists of calcium spikes superimposed on slower, periodic plateau depolarizations. As glucose level increases, the amplitudes of spikes and plateaus do not change, yet a pacemaker mechanism prolongs the plateau phases. The corresponding increase of calcium spike activity appears to mediate glucose-dependent calcium uptake. Our long term goals are to identify and charactrize the ionic mechanisms underlying the response, and to determine how they are controlled by glucose and its metabolism. Our working hypothesis proposes membrane ionic conductance mechanisms which may contribute to each of the four coupled electrical events noted above. To test this, we will use patch-clamp methods to study membrane currents through ATP-inhibited and calcium-activated potassium chanels as well as through a new voltage-dependent potassium channel, and to characterize inward currents through sodium and calcium channels.

胰腺B细胞的葡萄糖诱导的膜电活动介导 钙摄取用于胰岛素释放。 电响应发生在 两个葡萄糖依赖性相：随着葡萄糖水平从零增加到 胰岛素释放的阈值，有一个亚阈值去极化 B细胞膜。 其他葡萄糖触发胰岛素释放和 电动性。 电活动由钙尖峰组成 叠加在较慢的周期性高原去极化上。 作为葡萄糖水平 增加，尖峰和高原的幅度没有改变，但 起搏器机制延长了高原阶段。 相应 钙尖峰活性的增加似乎介导了葡萄糖依赖性 钙吸收。 我们的长期目标是识别和符合特征 离子机制是响应的基础，并确定它们的状况 由葡萄糖及其代谢控制。 我们的工作假设提出了膜离子电导机制 可能有助于上述四个耦合的电气事件中的每一个。 为了测试这一点，我们将使用斑块钳方法研究膜电流 通过ATP抑制和钙激活的钾香奈儿以及 通过新的依赖电压的钾通道，并表征 通过钠和钙通道向内电流。