Clearance of store-released Ca2+by the Na+-Ca2+exchanger is diminished in aortic smooth muscle from Na+-K+-ATPase α2-isoform gene-ablated mice

Lynch, Ronald M.; Weber, Craig; Nullmeyer, Kevin D.; Moore, Edwin D.W.; Rutgeerts, Paul

doi:10.1152/ajpheart.00855.2007

Cited by 28 publications

(42 citation statements)

References 33 publications

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“…In adult rat cardiac myocytes, inhibition of the ␣ 2 -isoform of Na ϩ -K ϩ -ATPase results in increased I NaCa and enhanced cardiac myocyte contractility (20), indicating intimate cross-talk between the ␣ 2 -isoform of Na ϩ -K ϩ -ATPase and NCX1 in the t-tubules. Similar intimate cross-talk between NCX1 and the ␣ 2 -isoform of Na ϩ -K ϩ -ATPase has also recently been demonstrated for mouse aortic smooth muscle cells (13). The observations that in rodent cardiac myocytes PLM regulates the ␣ 1 -isoform but not ␣ 2 -isoform of Na ϩ -K ϩ -ATPase, and that cross-talk occurs predominantly between the ␣ 2 -isoform of Na ϩ -K ϩ -ATPase and NCX1 in the t-tubules, support our hypothesis that PLM regulates cardiac contractility by mechanisms other than inhibition of Na ϩ -K ϩ -ATPase.…”

Section: Discussionsupporting

confidence: 69%

Regulation of cardiac myocyte contractility by phospholemman: Na⁺/Ca²⁺ exchange versus Na⁺-K⁺-ATPase

Song¹,

Zhang²,

Wang³

et al. 2008

American Journal of Physiology-Heart and Circulatory Physiology

104

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Phospholemman (PLM) regulates cardiac Na+/Ca2+ exchanger (NCX1) and Na+-K+-ATPase in cardiac myocytes. PLM, when phosphorylated at Ser68, disinhibits Na+-K+-ATPase but inhibits NCX1. PLM regulates cardiac contractility by modulating Na+-K+-ATPase and/or NCX1. In this study, we first demonstrated that adult mouse cardiac myocytes cultured for 48 h had normal surface membrane areas, t-tubules, and NCX1 and sarco(endo)plasmic reticulum Ca2+-ATPase levels, and retained near normal contractility, but α1-subunit of Na+-K+-ATPase was slightly decreased. Differences in contractility between myocytes isolated from wild-type (WT) and PLM knockout (KO) hearts were preserved after 48 h of culture. Infection with adenovirus expressing green fluorescent protein (GFP) did not affect contractility at 48 h. When WT PLM was overexpressed in PLM KO myocytes, contractility and cytosolic Ca2+ concentration ([Ca2+]i) transients reverted back to those observed in cultured WT myocytes. Both Na+-K+-ATPase current ( Ipump) and Na+/Ca2+ exchange current ( INaCa) in PLM KO myocytes rescued with WT PLM were depressed compared with PLM KO myocytes. Overexpressing the PLMS68E mutant (phosphomimetic) in PLM KO myocytes resulted in the suppression of INaCa but had no effect on Ipump. Contractility, [Ca2+]i transient amplitudes, and sarcoplasmic reticulum Ca2+ contents in PLM KO myocytes overexpressing the PLMS68E mutant were depressed compared with PLM KO myocytes overexpressing GFP. Overexpressing the PLMS68A mutant (mimicking unphosphorylated PLM) in PLM KO myocytes had no effect on INaCa but decreased Ipump. Contractility, [Ca2+]i transient amplitudes, and sarcoplasmic reticulum Ca2+ contents in PLM KO myocytes overexpressing the S68A mutant were similar to PLM KO myocytes overexpressing GFP. We conclude that at the single-myocyte level, PLM affects cardiac contractility and [Ca2+]i homeostasis primarily by its direct inhibitory effects on Na+/Ca2+ exchange.

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Section: Discussionsupporting

confidence: 69%

Regulation of cardiac myocyte contractility by phospholemman: Na⁺/Ca²⁺ exchange versus Na⁺-K⁺-ATPase

Song¹,

Zhang²,

Wang³

et al. 2008

American Journal of Physiology-Heart and Circulatory Physiology

104

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“…Therefore, the increase in [Ca 2C ] i secondary to ouabain inhibition of a4 is not due to Ca 2C internalization from the media through plasma membrane uptake mechanisms, but is rather due to a decrease in the clearance of the cation from the cell cytoplasm. The only transport mechanism that has been described for the elimination of Ca 2C from the cytosol and that is linked to the function of the Na,K-ATPase is the Na C /Ca 2C exchanger (NCX; Lynch et al 2008). In excitable cells, the function of the NCX heavily relies on the inward flux of Na C maintained by the Na,K-ATPase to release Ca 2C out of the cytoplasm (Zhang et al 2005).…”

Section: Discussionmentioning

confidence: 99%

Activity of the Na,K-ATPase α4 isoform is important for membrane potential, intracellular Ca2+, and pH to maintain motility in rat spermatozoa

Jiménez

Sánchez²,

Wertheimer³

et al. 2010

Reproduction

104

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While the function of the ubiquitous Na,K-ATPase a1 subunit has been well documented, the role of the sperm-specific a4 isoform of this ion transporter is less known. We have explored the importance of a4 in rat sperm physiology by taking advantage of the high sensitivity of this isoform for the inhibitor ouabain. Using concentrations that selectively block a4 activity, we found ouabain to reduce not only sperm total motility, but also multiple parameters of sperm movement, including progressive motility, straight line, curvilinear, and average path velocities, lateral head displacement, beat cross frequency, and linearity. According to a direct role of a4 in Na C transport, ouabain inhibition of a4 increased [Na C ] i in the male gametes. In addition, interference of a4 activity with ouabain produced cell membrane depolarization, diminished pH, and increased [Ca 2C ] i in spermatozoa. Inhibition of a4 was sufficient to cause all these effects and additional blockage of a1, the other Na,K-ATPase a isoform expressed in sperm, and higher doses of ouabain did not result in further changes in the cell parameters studied. These results show that a4 is the Na,K-ATPase isoform primarily involved in controlling the transmembrane Na C gradient in sperm, and that a4 activity is necessary for maintaining membrane potential, [Ca ] i , and acid-base balance suggests that their regulation is the mechanism by which a4 maintains motility of the male gametes.

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“…Reducing the activity of Na + /K + ATPase can increase [Ca 2+ ]i via effects on the NCX (Golovina, et al, 2003,Lynch, et al, 2008. There is also evidence that Na + /K + ATPase alpha-2 isoform knockout mice have increased [Ca 2+ ] stores (Lynch, et al, 2008). Furthermore, a reduction in the activity of this pump has been observed in central neurons of rats during aging (Benzi, et al, 1994, Murali, et al, 2008,Torlinska and Grochowalska, 2004.…”

Section: Ncx Mode Reversal May Contribute To the Age-related Changes mentioning

confidence: 98%

“…Interestingly, the activity of the Na + /K + ATPase is closely coupled with the activity and direction in which the NCX functions. Reducing the activity of Na + /K + ATPase can increase [Ca 2+ ]i via effects on the NCX (Golovina, et al, 2003,Lynch, et al, 2008. There is also evidence that Na + /K + ATPase alpha-2 isoform knockout mice have increased [Ca 2+ ] stores (Lynch, et al, 2008).…”

Section: Ncx Mode Reversal May Contribute To the Age-related Changes mentioning

confidence: 99%

A switch in the mode of the sodium/calcium exchanger underlies an age-related increase in the slow afterhyperpolarization

Scutt

Allen

Kemenes

et al. 2015

Neurobiology of Aging

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During aging, the Ca 2+ sensitive slow afterhyperpolarization (sAHP) of hippocampal neurons is known to increase in duration. This change has also been observed in the serotonergic cerebral giant cells (CGCs) of the pond snail Lymnaea stagnalis, but has yet to be characterized. In this paper, we confirm that there is a reduction in firing rate, an increase in the duration of the sAHP, and an alteration in the strength and speed of spike frequency adaptation (SFA) in the CGCs during aging, a finding that is compatible with an increase in a sAHP current. We go on to show that age-related changes in the kinetics of SFA are consistent with a reduction in Ca 2+ clearance from the cell, which we confirm with Ca 2+ imaging and pharmacological manipulation of the sodium calcium exchanger (NCX). These experiments suggest that the NCX may be switching to a reverse-mode configuration in the CGCs during aging.3

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Clearance of store-released Ca²⁺by the Na⁺-Ca²⁺exchanger is diminished in aortic smooth muscle from Na⁺-K⁺-ATPase α₂-isoform gene-ablated mice

Abstract: Lynch RM, Weber CS, Nullmeyer KD, Moore ED, Paul RJ. Clearance of store-released Ca 2ϩ by the Na ϩ -Ca 2ϩ exchanger is diminished in aortic smooth muscle from Na ϩ -K ϩ -ATPase ␣2-isoform gene-ablated mice.

Cited by 28 publications

References 33 publications

Regulation of cardiac myocyte contractility by phospholemman: Na⁺/Ca²⁺ exchange versus Na⁺-K⁺-ATPase

Regulation of cardiac myocyte contractility by phospholemman: Na⁺/Ca²⁺ exchange versus Na⁺-K⁺-ATPase

Activity of the Na,K-ATPase α4 isoform is important for membrane potential, intracellular Ca2+, and pH to maintain motility in rat spermatozoa

A switch in the mode of the sodium/calcium exchanger underlies an age-related increase in the slow afterhyperpolarization

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Clearance of store-released Ca2+by the Na+-Ca2+exchanger is diminished in aortic smooth muscle from Na+-K+-ATPase α2-isoform gene-ablated mice

Abstract: Lynch RM, Weber CS, Nullmeyer KD, Moore ED, Paul RJ. Clearance of store-released Ca 2ϩ by the Na ϩ -Ca 2ϩ exchanger is diminished in aortic smooth muscle from Na ϩ -K ϩ -ATPase ␣2-isoform gene-ablated mice.

Cited by 28 publications

References 33 publications

Regulation of cardiac myocyte contractility by phospholemman: Na+/Ca2+ exchange versus Na+-K+-ATPase

Regulation of cardiac myocyte contractility by phospholemman: Na+/Ca2+ exchange versus Na+-K+-ATPase

Activity of the Na,K-ATPase α4 isoform is important for membrane potential, intracellular Ca2+, and pH to maintain motility in rat spermatozoa

A switch in the mode of the sodium/calcium exchanger underlies an age-related increase in the slow afterhyperpolarization

Contact Info

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Resources

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Clearance of store-released Ca²⁺by the Na⁺-Ca²⁺exchanger is diminished in aortic smooth muscle from Na⁺-K⁺-ATPase α₂-isoform gene-ablated mice

Regulation of cardiac myocyte contractility by phospholemman: Na⁺/Ca²⁺ exchange versus Na⁺-K⁺-ATPase

Regulation of cardiac myocyte contractility by phospholemman: Na⁺/Ca²⁺ exchange versus Na⁺-K⁺-ATPase