The biochemistry and medical significance of the flavonoids.

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

Millions of years before we began to manipulate the flow of light using synthetic structures, biological systems were using nanometre-scale architectures to produce striking optical effects. An astonishing variety of natural photonic structures exists: a species of Brittlestar uses photonic elements composed of calcite to collect light, Morpho butterflies use multiple layers of cuticle and air to produce their striking blue colour and some insects use arrays of elements, known as nipple arrays, to reduce reflectivity in their compound eyes. Natural photonic structures are providing inspiration for technological applications.

Photonic structures in biology

The Na-K-ATPase is characterized by a complex molecular heterogeneity that results from the expression and differential association of multiple isoforms of both its α- and β-subunits. At present, a...

Isozymes of the Na-K-ATPase: heterogeneity in structure, diversity in function

▪ Abstract The Na,K-ATPase or sodium pump carries out the coupled extrusion and uptake of Na and K ions across the plasma membranes of cells of most higher eukaryotes. It is a member of the P-type ...

Biochemistry of Na,K-ATPase

https://www.utoledo.edu/med/depts/physpharm/pdfs/faculty/modyanov/1976.pdf

Transport and Pharmacological Properties of Nine Different Human Na,K-ATPase Isozymes

FXYD proteins belong to a family of small-membrane proteins. Recent experimental evidence suggests that at least five of the seven members of this family, FXYD1 (phospholemman), FXYD2 (γ-subunit of...

FXYD proteins: new regulators of Na-K-ATPase.

Na,K-ATPase and gastric and nongastric H,K-ATPases are the only P-type ATPases of higher organisms that are oligomeric and are associated with a beta subunit, which is obligatory for expression and function of enzymes. Topogenesis studies suggest that beta subunits have a fundamental and unique role in K+-transporting P-type ATPases in that they facilitate the correct membrane integration and packing of the catalytic a subunit of these P-type ATPases, which is necessary for their resistance to cellular degradation, their acquisition of functional properties, and their routing to the cell surface. In addition to this chaperone function, beta subunits also participate in the determination of intrinsic transport properties of Na,K- and H,K-ATPases. Increasing experimental evidence suggests that beta assembly is a highly ordered, beta isoform-specific process, which is mediated by multiple interaction sites that contribute in a coordinate, multistep process to the structural and functional maturation of Na,K- and H,K-ATPases.

The functional role of beta subunits in oligomeric P-type ATPases.

Purpose of reviewNa,K-ATPase is an oligomeric protein composed of α subunits, β subunits and FXYD proteins. The catalytic α subunit hydrolyzes ATP and transports the cations. Increasing experimental evidence suggest that β subunits and FXYD proteins essentially contribute to the variable physiologic

Functional roles of Na,K-ATPase subunits.

Voltage-dependent calcium (Ca2+) channels are involved in many specialized cellular functions1,2,3, and are controlled by intracellular signals such as heterotrimeric G-proteins4, protein kinases5,6 and calmodulin (CaM)7,8. However, the direct role of small G-proteins in the regulation of Ca2+ channels is unclear. We report here that the GTP-bound form of kir/Gem, identified originally as a Ras-related small G-protein that binds CaM9,10,11, inhibits high-voltage-activated Ca2+ channel activities by interacting directly with the β-subunit. The reduced channel activities are due to a decrease in α1-subunit expression at the plasma membrane. The binding of Ca2+/CaM to kir/Gem is required for this inhibitory effect by promoting the cytoplasmic localization of kir/Gem. Inhibition of L-type Ca2+ channels by kir/Gem prevents Ca2+-triggered exocytosis in hormone-secreting cells. We propose that the small G-protein kir/Gem, interacting with β-subunits, regulates Ca2+ channel expression at the cell surface.

Käthi Geering

Papers

Transport and Pharmacological Properties of Nine Different Human Na,K-ATPase Isozymes

FXYD proteins: new regulators of Na-K-ATPase.

The functional role of beta subunits in oligomeric P-type ATPases.

Functional roles of Na,K-ATPase subunits.

Regulation of Ca2+ channel expression at the cell surface by the small G-protein kir/Gem.