Localization of the Na+‐Ca2+ Exchanger in Vascular Smooth Muscle, and in Neurons and Astrocytesa

Juhaszova, Magdalena; Shimizu, Hiroshi; Borin, M. L.; Yip, Rick K.; Santiago, Eligio M.; Lindenmayer, George E.; Blaustein, Mordecai P.

doi:10.1111/j.1749-6632.1996.tb44804.x

Cited by 88 publications

(55 citation statements)

References 25 publications

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“…The location of the high affinity isoforms appears to provide a clue because the SR and ER sequester Ca 2ϩ , and the Ca 2ϩ released from these organelles controls numerous cell activities. A critical link between the Na ϩ pump and cell Ca 2ϩ is the PM Na ϩ ͞Ca 2ϩ exchanger, which is also localized to PM regions that overlie junctional SR and ER (11,14,15,31). The energy required to control cytosolic Ca 2ϩ via the Na ϩ ͞Ca 2ϩ exchanger is derived from the Na ϩ electrochemical gradient generated by the Na ϩ pump (12).…”

Section: Resultsmentioning

confidence: 99%

Na ⁺ pump low and high ouabain affinity α subunit isoforms are differently distributed in cells

Juhaszova

Blaustein

1997

Proc. Natl. Acad. Sci. U.S.A.

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Three isoforms (␣1, ␣2, and ␣3) of the catalytic (␣) subunit of the plasma membrane (PM) Na ؉ pump have been identified in the tissues of birds and mammals. These isoforms differ in their affinities for ions and for the Na ؉ pump inhibitor, ouabain. In the rat, ␣1 has an unusually low affinity for ouabain. The PM of most rat cells contains both low (␣1) and high (␣2 or ␣3) ouabain affinity isoforms, but precise localization of specific isoforms, and their functional significance, are unknown. We employed high resolution immunocytochemical techniques to localize ␣ subunit isoforms in primary cultured rat astrocytes, neurons, and arterial myocytes. Isoform ␣1 was ubiquitously distributed over the surfaces of these cells. In contrast, high ouabain affinity isoforms (␣2 in astrocytes, ␣3 in neurons and myocytes) were confined to a reticular distribution within the PM that paralleled underlying endoplasmic or sarcoplasmic reticulum. This distribution is identical to that of the PM Na͞Ca exchanger. This raises the possibility that ␣1 may regulate bulk cytosolic Na ؉ , whereas ␣2 and ␣3 may regulate Na ؉ and, indirectly, Ca 2؉ in a restricted cytosolic space between the PM and reticulum. The high ouabain affinity Na ؉ pumps may thereby modulate reticulum Ca 2؉ content and Ca 2؉ signaling.

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Section: Resultsmentioning

confidence: 99%

Na ⁺ pump low and high ouabain affinity α subunit isoforms are differently distributed in cells

Juhaszova

Blaustein

1997

Proc. Natl. Acad. Sci. U.S.A.

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280

246

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“…Notably, NCX1 (40) and TRPC channels (32) are confined to the PM microdomains that overlie the closely apposed junctional SR. Moreover, coimmunoprecipitation experiments provide evidence for the association of NCX1 with TRPC3 in protein complexes in HEK293 cells (63).…”

Section: Discussionmentioning

confidence: 99%

Upregulation of Na⁺/Ca²⁺exchanger and TRPC6 contributes to abnormal Ca²⁺homeostasis in arterial smooth muscle cells from Milan hypertensive rats

Zulian

Baryshnikov

Linde

et al. 2010

American Journal of Physiology-Heart and Circulatory Physiology

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Zulian A, Baryshnikov SG, Linde CI, Hamlyn JM, Ferrari P, Golovina VA. Upregulation of Na ϩ /Ca 2ϩ exchanger and TRPC6 contributes to abnormal Ca 2ϩ homeostasis in arterial smooth muscle cells from Milan hypertensive rats. Am J Physiol Heart Circ Physiol 299: H624 -H633, 2010. First published July 9, 2010; doi:10.1152/ajpheart.00356.2010.-The Milan hypertensive strain (MHS) of rats is a model for hypertension in humans. Inherited defects in renal function have been well studied in MHS rats, but the mechanisms that underlie the elevated vascular resistance are unclear. Altered Ca 2ϩ signaling plays a key role in the vascular dysfunction associated with arterial hypertension. Here we compared Ca 2ϩ signaling in mesenteric artery smooth muscle cells from MHS rats and its normotensive counterpart (MNS). Systolic blood pressure was higher in MHS than in MNS rats (144 Ϯ 2 vs. 113 Ϯ 1 mmHg, P Ͻ 0.05). Resting cytosolic free Ca 2ϩ concentration (measured with fura-2) and ATP-induced Ca 2ϩ transients were augmented in freshly dissociated arterial myocytes from MHS rats. Ba 2ϩ entry activated by the diacylglycerol analog 1-oleoyl-2-acetyl-sn-glycerol (a measure of receptor-operated channel activity) was much greater in MHS than MNS arterial myocytes. This correlated with a threefold upregulation of transient receptor potential canonical 6 (TRPC6) protein. TRPC3, the other component of receptor-operated channels, was marginally, but not significantly, upregulated. The expression of TRPC1/5, components of store-operated channels, was not altered in MHS mesenteric artery smooth muscle. Immunoblots also revealed that the Na ϩ /Ca 2ϩ exchanger-1 (NCX1) was greatly upregulated in MHS mesenteric artery (by ϳ13-fold), whereas the expression of plasma membrane Ca 2ϩ -ATPase was not altered. Ca 2ϩ entry via the reverse mode of NCX1 evoked by the removal of extracellular Na ϩ induced a rapid increase in cytosolic free Ca 2ϩ concentration that was significantly larger in MHS arterial myocytes. The expression of ␣ 1/␣2 Na ϩ pumps in MHS mesenteric arteries was not changed. Immunocytochemical observations showed that NCX1 and TRPC6 are clustered in plasma membrane microdomains adjacent to the underlying sarcoplasmic reticulum. In summary, MHS arteries exhibit upregulated TRPC6 and NCX1 and augmented Ca 2ϩ signaling. We suggest that the increased Ca 2ϩ signaling contributes to the enhanced vasoconstriction and elevated blood pressure in MHS rats.adducin; hypertension; Milan normotensive rats; C-type transient receptor potential channels; receptor-operated calcium entry PRIMARY OR ESSENTIAL HYPERTENSION is a multifactorial disorder resulting from the complex interplay between genetic predisposition (genetic heritability, ϳ30%) and multiple environmental factors (1,44,71,74). The major difficulty in identifying genes contributing to hypertension is the etiological heterogeneity of hypertension (1). Genetic, physiological, and biochemical studies reveal that an alteration in the genes encoding adducin, a ubiquitously expressed membrane-ske...

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“…The importance of a particular calcium clearance mechanism in the formation of the cellular response will depend on where the CCMs are expressed relative to the channels that initiate the response. We have not yet localized where NCXs are expressed in taste cells, but based on their contribution to the calcium influx signals, we predict they are closely associated with VGCCs at presynaptic nerve terminals as has been reported in other neurons (Juhaszova et al 1996;Luther et al 1992;Reuter and Porzig 1995).…”

Section: Ncxs Significantly Contribute To the Termination Of Calcium mentioning

confidence: 99%

Sodium/Calcium Exchangers Selectively Regulate Calcium Signaling in Mouse Taste Receptor Cells

Szebenyi

Laskowski

Medler

2010

Journal of Neurophysiology

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Localization of the Na⁺‐Ca²⁺ Exchanger in Vascular Smooth Muscle, and in Neurons and Astrocytes^a

Cited by 88 publications

References 25 publications

Na ⁺ pump low and high ouabain affinity α subunit isoforms are differently distributed in cells

Na ⁺ pump low and high ouabain affinity α subunit isoforms are differently distributed in cells

Upregulation of Na⁺/Ca²⁺exchanger and TRPC6 contributes to abnormal Ca²⁺homeostasis in arterial smooth muscle cells from Milan hypertensive rats

Sodium/Calcium Exchangers Selectively Regulate Calcium Signaling in Mouse Taste Receptor Cells

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Localization of the Na+‐Ca2+ Exchanger in Vascular Smooth Muscle, and in Neurons and Astrocytesa

Cited by 88 publications

References 25 publications

Na + pump low and high ouabain affinity α subunit isoforms are differently distributed in cells

Na + pump low and high ouabain affinity α subunit isoforms are differently distributed in cells

Upregulation of Na+/Ca2+exchanger and TRPC6 contributes to abnormal Ca2+homeostasis in arterial smooth muscle cells from Milan hypertensive rats

Sodium/Calcium Exchangers Selectively Regulate Calcium Signaling in Mouse Taste Receptor Cells

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Localization of the Na⁺‐Ca²⁺ Exchanger in Vascular Smooth Muscle, and in Neurons and Astrocytes^a

Na ⁺ pump low and high ouabain affinity α subunit isoforms are differently distributed in cells

Na ⁺ pump low and high ouabain affinity α subunit isoforms are differently distributed in cells

Upregulation of Na⁺/Ca²⁺exchanger and TRPC6 contributes to abnormal Ca²⁺homeostasis in arterial smooth muscle cells from Milan hypertensive rats