/pdf/inositol-trisphosphate-and-diacylglycerol-as-second-4drzjsg27y.pdf

Inositol trisphosphate and diacylglycerol as second messengers.

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

http://utsc.utoronto.ca/%7Ebritto/publications/amtox.pdf

NH4+ toxicity in higher plants: a critical review

Nitric Oxide Donors: Chemical Activities and Biological Applications

Electrophysiology of the pancreatic beta-cell.

The stimulus-secretion coupling of glucose-induced insulin release. XLVI. Physiological role of L-glutamine as a fuel for pancreatic islets.

Stimulus-secretion coupling of arginine-induced insulin release. Insulinotropic action of agmatine.

The mechanisms responsible for the stimulation of insulin release from the pancreatic beta-cell by hypoglycemic sulfonylureas are reviewed herein. One hypothesis postulates that these agents act, at the level of the plasma membrane, by causing the closure of a class of K+ channels characterized by their sensitivity to ATP. This may lead to depolarization of the plasma membrane, gating of voltage-sensitive Ca2+ channels, increase in cytosolic Ca2+ activity, and activation of the effector system for insulin release. However, it is not evident that the closure of ATP-sensitive K+ channels accounts for effects of sulfonylureas such as inhibition of K+ inflow into the islet cells, increase in their Na+ content, or even stimulation of Ca2+ inflow and insulin release at physiological or higher concentrations of D-glucose.

Mechanisms of sulfonylurea-induced insulin release.

3-(Alkylamino)-4h-Pyrido[4,3-E]-1,2,4-Thiadiazine 1,1-Dioxides as Powerful Inhibitors of Insulin Release from Rat Pancreatic B-Cells: A New Class of Potassium Channel Openers?

Insulin release and beta-cell membrane potentials in response to glucose at 37 and 27 degrees C have been measured simultaneously in single, micro-dissected, perifused islets of Langerhans from normal mice. Insulin release and 45Ca outflow in response to glucose at 37 and 27 degrees C have been measured simultaneously from perfused islets isolated by collagenase digestion from normal rats. The effect of cooling on beta-cell membrane potassium permeability was assessed by changes in measured membrane potential and input resistance (in the mouse) and by changes in 86Rb outflow (in the rat). Resting and active beta-cell membrane parameters (i.e. membrane potential, spike frequency, input resistance, 45Ca outflow and 86Rb outflow), in both mouse and rat islets, were affected only slightly by cooling to 27 degrees C, with temperature coefficients of 2 or lower. At 27 degrees C glucose-stimulated insulin release was inhibited completely in mouse islets and almost completely in rat islets. The temperature coefficients in both preparations were greater than 5. It is concluded that beta-cell electrical activity and changes in membrane permeability induced by glucose are not consequences of insulin release.

Philippe Lebrun

Papers

The stimulus-secretion coupling of glucose-induced insulin release. XLVI. Physiological role of L-glutamine as a fuel for pancreatic islets.

Stimulus-secretion coupling of arginine-induced insulin release. Insulinotropic action of agmatine.

Mechanisms of sulfonylurea-induced insulin release.

3-(Alkylamino)-4h-Pyrido[4,3-E]-1,2,4-Thiadiazine 1,1-Dioxides as Powerful Inhibitors of Insulin Release from Rat Pancreatic B-Cells: A New Class of Potassium Channel Openers?

Cooling dissociates glucose-induced insulin release from electrical activity and cation fluxes in rodent pancreatic islets.