Molecular mechanisms of pituitary endocrine cell calcium handling

Abstract

Endocrine pituitary cells express numerous voltage-gated Na+, Ca2+, K+, and Cl− channels and several ligand-gated channels, and they fire action potentials spontaneously. Depending on the cell type, this electrical activity can generate localized or global Ca2+ signals, the latter reaching the threshold for stimulus–secretion coupling. These cells also express numerous G-protein-coupled receptors, which can stimulate or silence electrical activity and Ca2+ influx through voltage-gated Ca2+ channels and hormone release. Receptors positively coupled to the adenylyl cyclase signaling pathway stimulate electrical activity with cAMP, which activates hyperpolarization-activated cyclic nucleotide-regulated channels directly, or by cAMP-dependent kinase-mediated phosphorylation of K+, Na+, Ca2+, and/or non-selective cation-conducting channels. Receptors that are negatively coupled to adenylyl cyclase signaling pathways inhibit spontaneous electrical activity and accompanied Ca2+ transients predominantly through the activation of inwardly rectifying K+ channels and the inhibition of voltage-gated Ca2+ channels. The Ca2+-mobilizing receptors activate inositol trisphosphate-gated Ca2+ channels in the endoplasmic reticulum, leading to Ca2+ release in an oscillatory or non-oscillatory manner, depending on the cell type. This Ca2+ release causes a cell type-specific modulation of electrical activity and intracellular Ca2+ handling.