Relationship between intracellular Na+ concentration and reduced Na+ affinity in Na+,K+-ATPase mutants causing neurological disease

Research output: Contribution to conferencePosterResearch

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Relationship between intracellular Na+ concentration and reduced Na+ affinity in Na+,K+-ATPase mutants causing neurological disease. / Toustrup-Jensen, Mads Schak; Einholm, Anja P.; Schack, Vivien; Nielsen, Hang Nguyen; Holm, Rikke; Sobrido, Maria-Jesus; Andersen, Jens Peter; Clausen, Torben; Vilsen, Bente.

2014. Poster session presented at 14th International ATPase Conference “Na,K‐ATPase and related transport ATPases: Structure, mechanism, cell biology, health and disease”, Lunteren, Netherlands.

Research output: Contribution to conferencePosterResearch

Harvard

Toustrup-Jensen, MS, Einholm, AP, Schack, V, Nielsen, HN, Holm, R, Sobrido, M-J, Andersen, JP, Clausen, T & Vilsen, B 2014, 'Relationship between intracellular Na+ concentration and reduced Na+ affinity in Na+,K+-ATPase mutants causing neurological disease', 14th International ATPase Conference “Na,K‐ATPase and related transport ATPases: Structure, mechanism, cell biology, health and disease”, Lunteren, Netherlands, 30/08/2014 - 05/09/2014.

APA

Toustrup-Jensen, M. S., Einholm, A. P., Schack, V., Nielsen, H. N., Holm, R., Sobrido, M-J., Andersen, J. P., Clausen, T., & Vilsen, B. (2014). Relationship between intracellular Na+ concentration and reduced Na+ affinity in Na+,K+-ATPase mutants causing neurological disease. Poster session presented at 14th International ATPase Conference “Na,K‐ATPase and related transport ATPases: Structure, mechanism, cell biology, health and disease”, Lunteren, Netherlands.

CBE

Toustrup-Jensen MS, Einholm AP, Schack V, Nielsen HN, Holm R, Sobrido M-J, Andersen JP, Clausen T, Vilsen B. 2014. Relationship between intracellular Na+ concentration and reduced Na+ affinity in Na+,K+-ATPase mutants causing neurological disease. Poster session presented at 14th International ATPase Conference “Na,K‐ATPase and related transport ATPases: Structure, mechanism, cell biology, health and disease”, Lunteren, Netherlands.

MLA

Toustrup-Jensen, Mads Schak et al. Relationship between intracellular Na+ concentration and reduced Na+ affinity in Na+,K+-ATPase mutants causing neurological disease. 14th International ATPase Conference “Na,K‐ATPase and related transport ATPases: Structure, mechanism, cell biology, health and disease”, 30 Aug 2014, Lunteren, Netherlands, Poster, 2014.

Vancouver

Toustrup-Jensen MS, Einholm AP, Schack V, Nielsen HN, Holm R, Sobrido M-J et al. Relationship between intracellular Na+ concentration and reduced Na+ affinity in Na+,K+-ATPase mutants causing neurological disease. 2014. Poster session presented at 14th International ATPase Conference “Na,K‐ATPase and related transport ATPases: Structure, mechanism, cell biology, health and disease”, Lunteren, Netherlands.

Author

Toustrup-Jensen, Mads Schak ; Einholm, Anja P. ; Schack, Vivien ; Nielsen, Hang Nguyen ; Holm, Rikke ; Sobrido, Maria-Jesus ; Andersen, Jens Peter ; Clausen, Torben ; Vilsen, Bente. / Relationship between intracellular Na+ concentration and reduced Na+ affinity in Na+,K+-ATPase mutants causing neurological disease. Poster session presented at 14th International ATPase Conference “Na,K‐ATPase and related transport ATPases: Structure, mechanism, cell biology, health and disease”, Lunteren, Netherlands.

Bibtex

@conference{a644d2eeb610489cafc33d98ece504f2,
title = "Relationship between intracellular Na+ concentration and reduced Na+ affinity in Na+,K+-ATPase mutants causing neurological disease",
abstract = "The neurological disorders familial hemiplegic migraine type 2 (FHM2), alternating hemiplegia of childhood (AHC), and rapid-onset dystonia parkinsonism (RDP) are caused by mutations of Na+,K+-ATPase α2 and α3 isoforms, expressed in glial and neuronal cells, respectively. Although these disorders are distinct, they overlap in phenotypical presentation. Two Na+,K+-ATPase mutations, extending the C terminus by either 28 residues ({"}+28{"} mutation) or an extra tyrosine ({"}+Y{"}), are associated with FHM2 and RDP, respectively. We describe here functional consequences of these and other neurological disease mutations as well as an extension of the C terminus only by a single alanine. The dependence of the mutational effects on the specific α isoform in which the mutation is introduced was furthermore studied. At the cellular level we have characterized the C-terminal extension mutants and other mutants, addressing the question to what extent they cause a change of the intracellular Na+ and K+ concentrations ([Na+]i and [K+]i) in COS cells. C-terminal extension mutants generally showed dramatically reduced Na+ affinity without disturbance of K+ binding, as did other RDP mutants. No phosphorylation from ATP was observed for the +28 mutation of α2 despite a high expression level. A significant rise of [Na+]i and reduction of [K+]i was detected in cells expressing mutants with reduced Na+ affinity and did not require a concomitant reduction of the maximal catalytic turnover rate or expression level. Moreover, two mutations that increase Na+ affinity were found to reduce [Na+]i. It is concluded that the Na+ affinity of the Na+,K+-ATPase is an important determinant of [Na+]i. ",
author = "Toustrup-Jensen, {Mads Schak} and Einholm, {Anja P.} and Vivien Schack and Nielsen, {Hang Nguyen} and Rikke Holm and Maria-Jesus Sobrido and Andersen, {Jens Peter} and Torben Clausen and Bente Vilsen",
year = "2014",
month = aug,
day = "30",
language = "English",
note = "null ; Conference date: 30-08-2014 Through 05-09-2014",

}

RIS

TY - CONF

T1 - Relationship between intracellular Na+ concentration and reduced Na+ affinity in Na+,K+-ATPase mutants causing neurological disease

AU - Toustrup-Jensen, Mads Schak

AU - Einholm, Anja P.

AU - Schack, Vivien

AU - Nielsen, Hang Nguyen

AU - Holm, Rikke

AU - Sobrido, Maria-Jesus

AU - Andersen, Jens Peter

AU - Clausen, Torben

AU - Vilsen, Bente

PY - 2014/8/30

Y1 - 2014/8/30

N2 - The neurological disorders familial hemiplegic migraine type 2 (FHM2), alternating hemiplegia of childhood (AHC), and rapid-onset dystonia parkinsonism (RDP) are caused by mutations of Na+,K+-ATPase α2 and α3 isoforms, expressed in glial and neuronal cells, respectively. Although these disorders are distinct, they overlap in phenotypical presentation. Two Na+,K+-ATPase mutations, extending the C terminus by either 28 residues ("+28" mutation) or an extra tyrosine ("+Y"), are associated with FHM2 and RDP, respectively. We describe here functional consequences of these and other neurological disease mutations as well as an extension of the C terminus only by a single alanine. The dependence of the mutational effects on the specific α isoform in which the mutation is introduced was furthermore studied. At the cellular level we have characterized the C-terminal extension mutants and other mutants, addressing the question to what extent they cause a change of the intracellular Na+ and K+ concentrations ([Na+]i and [K+]i) in COS cells. C-terminal extension mutants generally showed dramatically reduced Na+ affinity without disturbance of K+ binding, as did other RDP mutants. No phosphorylation from ATP was observed for the +28 mutation of α2 despite a high expression level. A significant rise of [Na+]i and reduction of [K+]i was detected in cells expressing mutants with reduced Na+ affinity and did not require a concomitant reduction of the maximal catalytic turnover rate or expression level. Moreover, two mutations that increase Na+ affinity were found to reduce [Na+]i. It is concluded that the Na+ affinity of the Na+,K+-ATPase is an important determinant of [Na+]i.

AB - The neurological disorders familial hemiplegic migraine type 2 (FHM2), alternating hemiplegia of childhood (AHC), and rapid-onset dystonia parkinsonism (RDP) are caused by mutations of Na+,K+-ATPase α2 and α3 isoforms, expressed in glial and neuronal cells, respectively. Although these disorders are distinct, they overlap in phenotypical presentation. Two Na+,K+-ATPase mutations, extending the C terminus by either 28 residues ("+28" mutation) or an extra tyrosine ("+Y"), are associated with FHM2 and RDP, respectively. We describe here functional consequences of these and other neurological disease mutations as well as an extension of the C terminus only by a single alanine. The dependence of the mutational effects on the specific α isoform in which the mutation is introduced was furthermore studied. At the cellular level we have characterized the C-terminal extension mutants and other mutants, addressing the question to what extent they cause a change of the intracellular Na+ and K+ concentrations ([Na+]i and [K+]i) in COS cells. C-terminal extension mutants generally showed dramatically reduced Na+ affinity without disturbance of K+ binding, as did other RDP mutants. No phosphorylation from ATP was observed for the +28 mutation of α2 despite a high expression level. A significant rise of [Na+]i and reduction of [K+]i was detected in cells expressing mutants with reduced Na+ affinity and did not require a concomitant reduction of the maximal catalytic turnover rate or expression level. Moreover, two mutations that increase Na+ affinity were found to reduce [Na+]i. It is concluded that the Na+ affinity of the Na+,K+-ATPase is an important determinant of [Na+]i.

M3 - Poster

Y2 - 30 August 2014 through 5 September 2014

ER -