Centre for Integrative Physiology, Edinburgh Medical School: Biomedical Sciences, University of Edinburgh, Edinburgh, EH89XD, UK.
Mol Cell Endocrinol. 2018 Mar 5;463:37-48. doi: 10.1016/j.mce.2017.06.003. Epub 2017 Jun 5.
In anterior pituitary endocrine cells, large (BK), small (SK) and intermediate (IK) conductance calcium activated potassium channels are key determinants in shaping cellular excitability in a cell type- and context-specific manner. Indeed, these channels are targeted by multiple signaling pathways that stimulate or inhibit cellular excitability. BK channels can, paradoxically, both promote electrical bursting as well as terminate bursting and spiking dependent upon intrinsic BK channel properties and proximity to voltage gated calcium channels in somatotrophs, lactotrophs and corticotrophs. In contrast, SK channels are predominantly activated by calcium released from intracellular IP3-sensitive calcium stores and mediate membrane hyperpolarization in cells including gonadotrophs and corticotrophs. IK channels are predominantly expressed in corticotrophs where they limit membrane excitability. A major challenge for the future is to determine the cell-type specific molecular composition of calcium-activated potassium channels and how they control anterior pituitary hormone secretion as well as other calcium-dependent processes.
在垂体前叶内分泌细胞中，大电导钙激活钾通道（BK）、小电导钙激活钾通道（SK）和中间电导钙激活钾通道（IK）是决定细胞兴奋性的关键因素，其方式具有细胞类型和背景的特异性。事实上，这些通道是多种信号通路的靶点，这些信号通路可以刺激或抑制细胞兴奋性。BK 通道可以矛盾地促进电爆发，也可以根据内在的 BK 通道特性和与 somatotrophs、lactotrophs 和 corticotrophs 中的电压门控钙通道的接近程度来终止爆发和尖峰。相比之下，SK 通道主要被细胞内 IP3 敏感钙库释放的钙激活，并介导包括 gonadotrophs 和 corticotrophs 在内的细胞的膜超极化。IK 通道主要在 corticotrophs 中表达，在 corticotrophs 中，它们限制膜兴奋性。未来的主要挑战是确定钙激活钾通道的细胞类型特异性分子组成，以及它们如何控制垂体前叶激素分泌以及其他依赖钙的过程。
