Na + -Ca2+ exchange

Additional cellular events linked to the activity of blood pressure regulating substances involve membrane sodium transport mechanisms Na+/K.+ ATPase Na+fLi countertransport Na+ -H exchange Na+-Ca2+ exchange Na+-K+ 2C1 transport passive Na+ transport potassium channels cell volume and intracellular pH changes and calcium channels. 

Sodium calcium exchanger Na+/Ca2+ exchanger Na+/Ca2+ antiporter NCX NCX1 NCX2 NCX3... 

The plasma membrane Na+/Ca2+ exchanger is a high-capacity and low affinity ionic transporter that exchanges three Na+ ions for one Ca2+ ion. When intracellular Ca2+ concentrations [Ca2+]i rise and the... 

Na+/Ca2+ exchanger activity is present in virtually evety cell type examined. The NCX1 gene is expressed in several tissues, including brain, heart, skeletal... 

An increase in [Na+]j can also regulate the Na+/Ca2+ exchanger. In particular, when intracellular Na+ increases, it binds to the transport site of the exchanger molecule, and after this Na+ influx, an inactivation process of the exchanger occurs. This inactivation process, very similar to the phenomenon occurring in voltage-dependent ionic channels, is named... 

Na+/Ca2+ Exchangers. Figure 2 Schematic diagram of NCX localization and function in a pre- and postsynaptic structure (Reproduced from Annunziato L, Pignataro G, Di Renzo GF (2004) Pharmacol Rev 56 633-654). 

Na /Caz+ Exchangers. Table 1 Regulatory mechanisms of Na+/Ca2+ exchanger activity... 

Na+/Ca2+ Exchangers. Figure 3 Potential steps in the pharmacological regulation of NCX isoform expression and activity. This scheme reproduces the potential levels at which drugs can interfere with the transduction, transcription, translation, and activity of NCX. 

Na+/Ca2 Exchangers. Table 2 Drug families inhibiting the Na+/Ca2+ exchanger... 

Na+/Ca2+ Exchangers. Figure 4 Molecular properties of drugs interacting with NCX. Scheme summarizing the potency, the mode of selectivity, the molecular site of action and the isoform specificity of drugs interfering with NCX activity. 

Na+/Ca2+ Exchangers. Figure 6 Chemical structures of some NCX inhibitors. IC50 values for NCX inhibition of drugs belonging to different chemical families. 

Iwamoto T (2004) Forefront of Na+/Ca2+ exchanger studies molecular pharmacology of Na+/Ca2+ exchange inhibitors. J Pharmacol Sci 96 27-32... 

Ryanodine leads to contracture of mammalian skeletal muscle, whereas it causes negative inotropism in cardiac muscle. This apparent opposite effects are due to difference in the Ca2+ extruding activity the released Ca2+ remains within cytoplasm in skeletal muscle because of low Ca2+ extruding activity, whereas the increased cytoplasmic Ca2+ is rapidly excluded out of the cytoplasm in cardiac muscle via Na+ -Ca2+ -exchange. 

Ca2+ pumps are needed for the removal of calcium from cells, as in the maintenance of low Ca2+ levels in resting muscle, in bone deposition, and in biomineralization. The Na+/Ca2+ exchanger and Ca2+-ATPase (a Ca2+/H+-exchanger) act in parallel to pump Ca2+ across membranes, the latter being considerably more effective than the former. X-ray structure determinations have been carried out both for Ca2+-ATPase and for its Ca2+-bound form (443). The latter contains two Ca2+ ions... 

Na+,Ca2+ exchangers are important for rapidly lowering high pulses of cytoplasmic Ca2+ 87... 

In tissue culture, astrocytes, hippocampal neurons and arterial myocytes all express al diffusely in their plas-malemma. In contrast, immunocytochemically stained a2 in astroglia and a3 in myocytes and neurons display reticular patterns and colocalize with the Na+/Ca2+ exchanger (NCX) (Fig. 5-6). These plasmalemma reticular patterns coincide with the patterns of staining for junctional complexes on sarcoplasmic reticulum and, in astroglia and neurons, junctional complexes on endoplasmic reticulum [23]. 

Genetic evidence supports the importance of coordinated expression and distributions of a2 or a3 Na+/K+ pump isoforms with the Na+/Ca2+ exchanger (NCX) and Ca2+ pumps to function in excitable and contractile cells deletion of one copy of the a2 Na+/K+ pump gene in mice leads to increased contractile force in cardiac and skeletal muscle while deletion of one copy of the al gene leads to reduction of contractile force [25]. In rat optic nerve astrocytes, deletion of the a2 gene or ouabain treatment of cells expressing a2 leads to increased capacitative calcium entrance responses, which reflect a decreased ability to rapidly remove cytosolic Ca2+ [26]. 

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