In electrically nonexcitable cells, Ca2+ influx is essential for regulating a host of kinetically distinct processes involving exocytosis, enzyme control, gene regulation, cell growth and prolifera...

Store-operated calcium channels.

The Na+/Ca2+ exchanger, an ion transport protein, is expressed in the plasma membrane (PM) of virtually all animal cells. It extrudes Ca2+ in parallel with the PM ATP-driven Ca2+ pump. As a reversible transporter, it also mediates Ca2+ entry in parallel with various ion channels. The energy for net Ca2+ transport by the Na+/Ca2+ exchanger and its direction depend on the Na+, Ca2+, and K+ gradients across the PM, the membrane potential, and the transport stoichiometry. In most cells, three Na+ are exchanged for one Ca2+. In vertebrate photoreceptors, some neurons, and certain other cells, K+ is transported in the same direction as Ca2+, with a coupling ratio of four Na+ to one Ca2+ plus one K+. The exchanger kinetics are affected by nontransported Ca2+, Na+, protons, ATP, and diverse other modulators. Five genes that code for the exchangers have been identified in mammals: three in the Na+/Ca2+ exchanger family (NCX1, NCX2, and NCX3) and two in the Na+/Ca2+ plus K+ family (NCKX1 and NCKX2). Genes homologous to NCX1 have been identified in frog, squid, lobster, and Drosophila. In mammals, alternatively spliced variants of NCX1 have been identified; dominant expression of these variants is cell type specific, which suggests that the variations are involved in targeting and/or functional differences. In cardiac myocytes, and probably other cell types, the exchanger serves a housekeeping role by maintaining a low intracellular Ca2+ concentration; its possible role in cardiac excitation-contraction coupling is controversial. Cellular increases in Na+ concentration lead to increases in Ca2+ concentration mediated by the Na+/Ca2+ exchanger; this is important in the therapeutic action of cardiotonic steroids like digitalis. Similarly, alterations of Na+ and Ca2+ apparently modulate basolateral K+ conductance in some epithelia, signaling in some special sense organs (e.g., photoreceptors and olfactory receptors) and Ca2+-dependent secretion in neurons and in many secretory cells. The juxtaposition of PM and sarco(endo)plasmic reticulum membranes may permit the PM Na+/Ca2+ exchanger to regulate sarco(endo)plasmic reticulum Ca2+ stores and influence cellular Ca2+ signaling.

https://www.physiology.org/doi/pdf/10.1152/physrev.1999.79.3.763

Sodium/Calcium Exchange: Its Physiological Implications

The mechanism regulating the production of steroids in response to trophic hormone stimulation has been the subject of investigation for over three decades. When considering the effects of trophic hormones on the steroidogenic process it is necessary to first distinguish between acute effects and chronic effects. Acute effects are those which result in the very rapid (within minutes) synthesis and secretion of steroids in response to hormone stimulation and involve the rapid translocation of intracellular cholesterol to the site of its cleavage, as will be discussed later. Chronic effects are those which occur on the order of hours to tens of hours and involve increased gene transcription and translation of the proteins involved in the biosynthesis of steroids. This chapter will focus on studies designed to elucidate the mechanisms involved in the acute regulation of steroid production in response to hormone stimulation. Overviews of the effects of chronic stimulation on steroidogenic enzymes have appeared in several excellent review articles (Simpson and Waterman 1983; Miller 1988; Hanukoglu 1992).

Regulation of the acute production of steroids in steroidogenic cells.

Activin, a member of the transforming growth factor beta protein family, was originally isolated from gonadal fluids and stimulates the release of pituitary follicle-stimulating hormone (FSH). Activin has numerous functions in both normal and neoplastic cells. Various cells synthesize activin and have a specific binding site for this peptide. However, the molecular basis for its actions is unknown. A binding protein for activin was purified from rat ovary and was identical to follistatin, a specific inhibitor of FSH release. It is likely that the binding protein participates in the diverse regulatory actions of activin.

https://science.sciencemag.org/content/sci/247/4944/836.full.pdf

Activin-binding protein from rat ovary is follistatin

Publisher Summary This chapter discusses the insulin-like growth factor (IGF) binding proteins—namely, IGF-I and IGF-II The IGFs are purified from human plasma and cell culture medium by virtue of their ability to stimulate the growth of cartilage or cultured fibroblasts, or their insulin-like activity The IGFs are synthesized in many fetal and postnatal tissues and are capable of acting locally IGF-I and IGF-II are single-chain 75-kDa polypeptides that are chemically related to insulin They bind with high affinity to IGF-I receptors that are thought to mediate most of their biological actions The IGF-I receptor is a homolog of the insulin receptor, having a heterotetrameric structure and a tyrosine kinase domain in the cytoplasmic portion of the β-subunit that phosphorylates the receptor and other substrates, and presumably is involved in transmembrane signaling Hybrid receptors consisting of one αβ IGF-I receptor heterodimer and one αβ insulin receptor heterodimer are described IGF-II also binds with high affinity to the IGF-II/Mannose 6-phosphate receptor IGF-II added with the IGF-II/Mannose 6-phosphate receptor stimulated the activation of the guanosine triphosphate (GTP) binding protein G i-2  The IGFs participate in the physiological growth of the developing child, fetus, and embryo

Insulin-like growth factor binding proteins.

Insulin-like growth factor II stimulates calcium influx in competent BALB/c 3T3 cells primed with epidermal growth factor. Characteristics of calcium influx and involvement of GTP-binding protein.

Itaru Kojima

Papers

Insulin-like growth factor II stimulates calcium influx in competent BALB/c 3T3 cells primed with epidermal growth factor. Characteristics of calcium influx and involvement of GTP-binding protein.

Calcium influx: an intracellular message of the mitogenic action of insulin-like growth factor-I.

A novel action of activin A: stimulation of insulin secretion in rat pancreatic islets.

Activin-A: A modulator of multiple types of anterior pituitary cells

Involvement of endogenous digitalis-like substance in genesis of deoxycorticosterone-salt hypertension.