Ion Channels and Signaling in the Pituitary Gland

Endocrine pituitary cells are neuronlike; they express numerous voltage-gated sodium, calcium, potassium, and chloride channels and fire action potentials spontaneously, accompanied by a rise in intracellular calcium. In some cells, spontaneous electrical activity is sufficient to drive the intracellular calcium concentration above the threshold for stimulus-secretion and stimulus-transcription coupling. In others, the function of these action potentials is to maintain the cells in a responsive state with cytosolic calcium near, but below, the threshold level. Some pituitary cells also express gap junction channels, which could be used for intercellular Ca 2 signaling in these cells. Endocrine cells also express extracellular ligand-gated ion channels, and their activation by hypothalamic and intrapituitary hormones leads to amplification of the pacemaking activity and facilitation of calcium influx and hormone release. These cells also express numerous G protein-coupled receptors, which can stimulate or silence electrical activity and action potential-dependent calcium influx and hormone release. Other members of this receptor family can activate calcium channels in the endoplasmic reticulum, leading to a cell type-specific modulation of electrical activity. This review summarizes recent findings in this field and our current understanding of the complex relationship between voltage-gated ion channels, ligand-gated ion channels, gap junction channels, and G protein-coupled receptors in pituitary cells. (Endocrine Reviews 31: 845-915, 2010) I. Introduction II. Pituitary Cell Types A. POMC-producing cells B. Heterodimeric glucoprotein-producing cells C. GH-and PRL-producing cells D. Nonsecretory cells III. Ion Channels Expressed in Pituitary Cells A. Voltage-gated channels B. Chloride channels and transporters C. Channels expressed in and controlled by the endoplasmic reticulum IV. Spontaneous Electrical Activity A. Spiking and bursting B. Pacemaking mechanisms C. Channels involved in spike depolarization D. A mechanism for bursting E. Functional roles of spontaneous spiking V. Signaling by Gap Junction Channels A. Connexins B. Pannexins VI. Signaling by Receptor Channels A. Cys-loop family of receptor channels B. Glutamate receptor channels C. Purinergic receptor channels VII. Role of GPCRs in the Regulation of Electrical Activity A. Stimulation of electrical activity by GPCRs B. Inhibition of electrical activity by GPCRs VIII. Calcium-Mobilizing Receptors and Electrical Activity A. The dynamics of Ca 2 release B. Calcium mobilization and secretion IX.