Transient Receptor Potential Channel 6–Mediated, Localized Cytosolic [Na
 +
 ] Transients Drive Na
 +
 /Ca
 2+
 Exchanger–Mediated Ca
 2+
 Entry in Purinergically Stimulated Aorta Smooth Muscle Cells

Poburko, Damon; Liao, Chiu-Hsiang; Lemos, Virgı́nia S.; Lin, Eric; Maruyama, Yoshiaki; Cole, William C.; Breemen, Cornelis van

doi:10.1161/circresaha.107.155531

Cited by 130 publications

(119 citation statements)

References 53 publications

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“…5B). This is consistent with a functional linkage of ROCs to NCX1 and ␣ 2 -Na ϩ pumps in rodents (34,46,49).…”

Section: Expression Of Nasupporting

confidence: 86%

“…These Na ϩ and Ca 2ϩ transporter protein distribution patterns are very similar to those in rodent arterial myocytes and some other cell types (26,31,39,46,48,54). The implication of this structural organization, consisting of units (plasmerosomes) of PM microdomains closely opposed to junctional SR, is that the ␣ 2 -Na ϩ pumps, NCX1 and ROCs (of which TRPC6 proteins are components), and the SR are also functionally linked (8).…”

Section: A B C D Esupporting

confidence: 58%

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Nanomolar ouabain increases NCX1 expression and enhances Ca²⁺signaling in human arterial myocytes: a mechanism that links salt to increased vascular resistance?

Linde

Antos

Golovina

et al. 2012

American Journal of Physiology-Heart and Circulatory Physiology

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Linde CI, Antos LK, Golovina VA, Blaustein MP. Nanomolar ouabain increases NCX1 expression and enhances Ca 2ϩ signaling in human arterial myocytes: a mechanism that links salt to increased vascular resistance? Am J Physiol Heart Circ Physiol 303: H784 -H794, 2012. First published July 27, 2012; doi:10.1152/ajpheart.00399.2012.-The mechanisms by which NaCl raises blood pressure (BP) in hypertension are unresolved, but much evidence indicates that endogenous ouabain is involved. In rodents, arterial smooth muscle cell (ASMC) Na ϩ pumps with an ␣2-catalytic subunit (ouabain EC50 Յ1.0 nM) are crucial for some hypertension models, even though Ϸ80% of ASMC Na ϩ pumps have an ␣1-subunit (ouabain EC50 Ϸ 5 M). Human ␣1-Na ϩ pumps, however, have high ouabain affinity (EC50 Ϸ 10 -20 nM). We used immunoblotting, immunocytochemistry, and Ca 2ϩ imaging (fura-2) to examine the expression, distribution, and function of Na ϩ pump ␣-subunit isoforms in human arteries and primary cultured human ASMCs (hASMCs). hASMCs express ␣1-and ␣2-Na ϩ pumps. Further, ␣2-, but not ␣1-, pumps are confined to plasma membrane microdomains adjacent to sarcoplasmic reticulum (SR), where they colocalize with Na/Ca exchanger-1 (NCX1) and C-type transient receptor potential-6 (receptor-operated channels, ROCs). Prolonged inhibition (72 h) with 100 nM ouabain (blocks nearly all ␣1-and ␣2-pumps) was toxic to most cultured hASMCs. Treatment with 10 nM ouabain (72 h), however, increased NCX1 and sarco(endo)plasmic reticulum Ca 2ϩ -ATPase expression and augmented ATP (10 M)-induced SR Ca 2ϩ release in 0 Ca 2ϩ , ouabain-free media, and Ca 2ϩ influx after external Ca 2ϩ restoration. The latter was likely mediated primarily by ROCs and store-operated Ca 2ϩ channels. These hASMC protein expression and Ca 2ϩ signaling changes are comparable with previous observations on myocytes isolated from arteries of many rat hypertension models. We conclude that the same structurally and functionally coupled mechanisms (␣2-Na ϩ pumps, NCX1, ROCs, and the SR) regulate Ca 2ϩ homeostasis and signaling in hASMCs and rodent ASMCs. These ouabain/endogenous ouabainmodulated mechanisms underlie the whole body autoregulation associated with increased vascular resistance and elevation of BP in human, salt-sensitive hypertension. human artery; ␣ 2-Na ϩ pumps; ouabain; Na/Ca exchanger-1; sarco-(endo)plasmic reticulum Ca 2ϩ -ATPase; receptor-operated channels THE ROLE OF SALT IN THE PATHOGENESIS of human essential hypertension is widely accepted, but the specific mechanisms by which salt elevates blood pressure (BP) are still poorly understood (28). Numerous studies link hypertension in rodents to elevated plasma endogenous ouabain (EO), an adrenocortical hormone (6, 24, 30), and to Na ϩ pumps with high affinity for ouabain (12,38,61). Increased expression and function of arterial myocyte Na/Ca exchanger-1 (NCX1) and cation channels with C-type transient receptor potential (TRPC) subunits are also involved (7,17,25,34,49,66). We have speculated that similar mechanisms are involved in h...

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“…5B). This is consistent with a functional linkage of ROCs to NCX1 and ␣ 2 -Na ϩ pumps in rodents (34,46,49).…”

Section: Expression Of Nasupporting

confidence: 86%

Section: A B C D Esupporting

confidence: 58%

Nanomolar ouabain increases NCX1 expression and enhances Ca²⁺signaling in human arterial myocytes: a mechanism that links salt to increased vascular resistance?

Linde

Antos

Golovina

et al. 2012

American Journal of Physiology-Heart and Circulatory Physiology

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show abstract

“…Here, we showed that human pancreatic cancer cells express TRPC1, 4, and 6 but not other isoforms. TRPC1 is believed to be a functional SOC in other cell types, including intestinal epithelial cells (38,48), and TRPC6 to be a functional receptor-operated channel (ROC) (34,45). Moreover, our data from the use of TRPC1 and NCX1 siRNAs strongly suggest coupling of TRPC1-encoded SOC and NCX1 in regulating human pancreatic cancer cell motility.…”

Section: Discussionmentioning

confidence: 74%

Molecular mechanisms underlying Ca²⁺-mediated motility of human pancreatic duct cells

Dong

Shim²,

et al. 2010

American Journal of Physiology-Cell Physiology

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“…The direction of NCX-mediated Ca 2+ movement depends on membrane potential and/or cytosolic Na + or Ca 2+ concentration (3). During adrenergic and purinergic stimulations, Na + entry through NSCC has been shown to drive NCX-mediated Ca 2+ entry in vascular smooth muscle (4,5). In addition, the Ca 2+ entry mode of NCX has been proposed to contribute to the increased vascular tone in salt-sensitive hypertensive rats (6).…”

Section: /Camentioning

confidence: 99%

Role of Na+/Ca2+ Exchanger–Mediated Ca2+ Entry in Pressure-Induced Myogenic Constriction in Rat Posterior Cerebral Arteries

et al. 2009

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Abstract. The involvement of Ca2+ entry via the Na + /Ca 2+ exchanger (NCX) in myogenic constriction of rat posterior cerebral arteries was investigated. RT-PCR identified mRNA for NCX1, 2, and 3 in the arteries. Na] i , which was reduced by the NCX inhibitor SEA0400. SEA0400 inhibited the development, but not the steady-state, of pressureinduced myogenic constriction, whereas it decreased both the initial and sustained phases of [Ca 2+ ] i elevation. These results suggest that Ca 2+ entry via NCX is involved in the development, but not the steady-state, of pressure-induced myogenic constriction.

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Transient Receptor Potential Channel 6–Mediated, Localized Cytosolic [Na ⁺ ] Transients Drive Na ⁺ /Ca ²⁺ Exchanger–Mediated Ca ²⁺ Entry in Purinergically Stimulated Aorta Smooth Muscle Cells

Cited by 130 publications

References 53 publications

Nanomolar ouabain increases NCX1 expression and enhances Ca²⁺signaling in human arterial myocytes: a mechanism that links salt to increased vascular resistance?

Nanomolar ouabain increases NCX1 expression and enhances Ca²⁺signaling in human arterial myocytes: a mechanism that links salt to increased vascular resistance?

Molecular mechanisms underlying Ca²⁺-mediated motility of human pancreatic duct cells

Role of Na+/Ca2+ Exchanger–Mediated Ca2+ Entry in Pressure-Induced Myogenic Constriction in Rat Posterior Cerebral Arteries

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Transient Receptor Potential Channel 6–Mediated, Localized Cytosolic [Na + ] Transients Drive Na + /Ca 2+ Exchanger–Mediated Ca 2+ Entry in Purinergically Stimulated Aorta Smooth Muscle Cells

Cited by 130 publications

References 53 publications

Nanomolar ouabain increases NCX1 expression and enhances Ca2+signaling in human arterial myocytes: a mechanism that links salt to increased vascular resistance?

Nanomolar ouabain increases NCX1 expression and enhances Ca2+signaling in human arterial myocytes: a mechanism that links salt to increased vascular resistance?

Molecular mechanisms underlying Ca2+-mediated motility of human pancreatic duct cells

Role of Na+/Ca2+ Exchanger–Mediated Ca2+ Entry in Pressure-Induced Myogenic Constriction in Rat Posterior Cerebral Arteries

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Product

Resources

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Transient Receptor Potential Channel 6–Mediated, Localized Cytosolic [Na ⁺ ] Transients Drive Na ⁺ /Ca ²⁺ Exchanger–Mediated Ca ²⁺ Entry in Purinergically Stimulated Aorta Smooth Muscle Cells

Nanomolar ouabain increases NCX1 expression and enhances Ca²⁺signaling in human arterial myocytes: a mechanism that links salt to increased vascular resistance?

Nanomolar ouabain increases NCX1 expression and enhances Ca²⁺signaling in human arterial myocytes: a mechanism that links salt to increased vascular resistance?

Molecular mechanisms underlying Ca²⁺-mediated motility of human pancreatic duct cells