ISLET CELL ELECTRICAL PACEMAKER MECHANISMS

葡萄糖诱导的胰腺B细胞膜电活动介导 用于胰岛素释放的钙摄取。 电反应发生在 两个葡萄糖依赖性阶段：当葡萄糖水平从零增加到 对于胰岛素释放的阈值，存在亚阈值去极化， B细胞膜。 额外的葡萄糖触发胰岛素释放， 电活性 电活动由钙峰组成 叠加在较慢的周期性平台去极化上。 As葡萄糖水平 增加，尖峰和平台的幅度不改变，但 起搏机制维持平台期。 相应的 钙峰活性增加似乎介导葡萄糖依赖性 钙摄取 我们的长期目标是识别和表征 反应背后的离子机制，并确定它们是如何 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， 可以对上述四个耦合电事件中的每一个做出贡献。 为了验证这一点，我们将使用膜片钳方法来研究膜电流 通过ATP抑制和钙激活钾通道以及 通过一个新的电压依赖性钾通道，并表征 通过钠和钙通道的内向电流。

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.