Overexpression of the Na/Ca. exchanger shapes stimulus-induced cytosolic Ca2+ oscillations in insulin-producing BRIN-BD11 cells

F Van Eylen, OD Horta, A Barez, A Kamagate, Peter Flatt, R Macianskiene, K Mubagwa, A Herchuelz

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Abstract

In response to glucose, mouse beta-cells display slow oscillations of the membrane potential and cytosolic free Ca2+ concentration ([Ca2+](i))whereas rat beta-cells display a staircase increase in these parameters. Mouse and rat islet cells differ also by their level of Na/Ca exchanger (NCX) activity. The view that the inward current generated by Na/Ca exchange shapes stimulus-induced electrical activity and [Ca2+](i) oscillations in pancreatic beta-cells was examined in insulin-producing BRIN-BD11 cells overexpressing the Na/Ca exchanger BRIN-BD11 cells were stably transfected with NCX1.7, one of the exchanger isoforms identified in the beta-cell. Overexpression could be assessed at the mRNA and protein level. Appropriate targeting to the plasma membrane could be assessed by microfluorescence and the increase in Na/Ca exchange activity. In response to K+, overexpressing cells showed a more rapid increase in [Ca2+](i) on membrane depolarization as well as a more rapid decrease of [Ca2+](i) on membrane repolarization. In response to glucose and tolbutamide, control BRIN cells showed large amplitude [Ca2+](i) oscillations. In, contrast, overexpressing cells showed a staircase increasein[Ca2+](i) without such large oscillations. Diazoxide-induced membrane hyperpolarization restored large amplitude [Ca2+](i) oscillations in overexpressing cells. The present data confirm that Na/Ca exchange plays a significant role in the rat beta-cell [Ca2+](i) homeostasis, the exchanger being a versatile system allowing both Ca2+ entry and outflow. Our data suggest that the current generated by the exchanger shapes stimulus-induced membrane potential and [Ca2+](i) oscillations in insulin-secreting cells, with the difference in electrical activity and [Ca2+](i) behavior seen in mouse and rat beta-cells resulting in part from a difference in Na/Ca exchange activity between these two cells.
LanguageEnglish
Pages366-375
JournalDiabetes
Volume51
Issue number2
Publication statusPublished - Feb 2002

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Insulin
Insulin-Secreting Cells
Membrane Potentials
Membranes
Diazoxide
Glucose
Tolbutamide
Islets of Langerhans
Protein Isoforms
Homeostasis
Cell Membrane
Messenger RNA

Cite this

Van Eylen, F., Horta, OD., Barez, A., Kamagate, A., Flatt, P., Macianskiene, R., ... Herchuelz, A. (2002). Overexpression of the Na/Ca. exchanger shapes stimulus-induced cytosolic Ca2+ oscillations in insulin-producing BRIN-BD11 cells. Diabetes, 51(2), 366-375.
Van Eylen, F ; Horta, OD ; Barez, A ; Kamagate, A ; Flatt, Peter ; Macianskiene, R ; Mubagwa, K ; Herchuelz, A. / Overexpression of the Na/Ca. exchanger shapes stimulus-induced cytosolic Ca2+ oscillations in insulin-producing BRIN-BD11 cells. In: Diabetes. 2002 ; Vol. 51, No. 2. pp. 366-375.
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abstract = "In response to glucose, mouse beta-cells display slow oscillations of the membrane potential and cytosolic free Ca2+ concentration ([Ca2+](i))whereas rat beta-cells display a staircase increase in these parameters. Mouse and rat islet cells differ also by their level of Na/Ca exchanger (NCX) activity. The view that the inward current generated by Na/Ca exchange shapes stimulus-induced electrical activity and [Ca2+](i) oscillations in pancreatic beta-cells was examined in insulin-producing BRIN-BD11 cells overexpressing the Na/Ca exchanger BRIN-BD11 cells were stably transfected with NCX1.7, one of the exchanger isoforms identified in the beta-cell. Overexpression could be assessed at the mRNA and protein level. Appropriate targeting to the plasma membrane could be assessed by microfluorescence and the increase in Na/Ca exchange activity. In response to K+, overexpressing cells showed a more rapid increase in [Ca2+](i) on membrane depolarization as well as a more rapid decrease of [Ca2+](i) on membrane repolarization. In response to glucose and tolbutamide, control BRIN cells showed large amplitude [Ca2+](i) oscillations. In, contrast, overexpressing cells showed a staircase increasein[Ca2+](i) without such large oscillations. Diazoxide-induced membrane hyperpolarization restored large amplitude [Ca2+](i) oscillations in overexpressing cells. The present data confirm that Na/Ca exchange plays a significant role in the rat beta-cell [Ca2+](i) homeostasis, the exchanger being a versatile system allowing both Ca2+ entry and outflow. Our data suggest that the current generated by the exchanger shapes stimulus-induced membrane potential and [Ca2+](i) oscillations in insulin-secreting cells, with the difference in electrical activity and [Ca2+](i) behavior seen in mouse and rat beta-cells resulting in part from a difference in Na/Ca exchange activity between these two cells.",
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Van Eylen, F, Horta, OD, Barez, A, Kamagate, A, Flatt, P, Macianskiene, R, Mubagwa, K & Herchuelz, A 2002, 'Overexpression of the Na/Ca. exchanger shapes stimulus-induced cytosolic Ca2+ oscillations in insulin-producing BRIN-BD11 cells', Diabetes, vol. 51, no. 2, pp. 366-375.

Overexpression of the Na/Ca. exchanger shapes stimulus-induced cytosolic Ca2+ oscillations in insulin-producing BRIN-BD11 cells. / Van Eylen, F; Horta, OD; Barez, A; Kamagate, A; Flatt, Peter; Macianskiene, R; Mubagwa, K; Herchuelz, A.

In: Diabetes, Vol. 51, No. 2, 02.2002, p. 366-375.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Overexpression of the Na/Ca. exchanger shapes stimulus-induced cytosolic Ca2+ oscillations in insulin-producing BRIN-BD11 cells

AU - Van Eylen, F

AU - Horta, OD

AU - Barez, A

AU - Kamagate, A

AU - Flatt, Peter

AU - Macianskiene, R

AU - Mubagwa, K

AU - Herchuelz, A

PY - 2002/2

Y1 - 2002/2

N2 - In response to glucose, mouse beta-cells display slow oscillations of the membrane potential and cytosolic free Ca2+ concentration ([Ca2+](i))whereas rat beta-cells display a staircase increase in these parameters. Mouse and rat islet cells differ also by their level of Na/Ca exchanger (NCX) activity. The view that the inward current generated by Na/Ca exchange shapes stimulus-induced electrical activity and [Ca2+](i) oscillations in pancreatic beta-cells was examined in insulin-producing BRIN-BD11 cells overexpressing the Na/Ca exchanger BRIN-BD11 cells were stably transfected with NCX1.7, one of the exchanger isoforms identified in the beta-cell. Overexpression could be assessed at the mRNA and protein level. Appropriate targeting to the plasma membrane could be assessed by microfluorescence and the increase in Na/Ca exchange activity. In response to K+, overexpressing cells showed a more rapid increase in [Ca2+](i) on membrane depolarization as well as a more rapid decrease of [Ca2+](i) on membrane repolarization. In response to glucose and tolbutamide, control BRIN cells showed large amplitude [Ca2+](i) oscillations. In, contrast, overexpressing cells showed a staircase increasein[Ca2+](i) without such large oscillations. Diazoxide-induced membrane hyperpolarization restored large amplitude [Ca2+](i) oscillations in overexpressing cells. The present data confirm that Na/Ca exchange plays a significant role in the rat beta-cell [Ca2+](i) homeostasis, the exchanger being a versatile system allowing both Ca2+ entry and outflow. Our data suggest that the current generated by the exchanger shapes stimulus-induced membrane potential and [Ca2+](i) oscillations in insulin-secreting cells, with the difference in electrical activity and [Ca2+](i) behavior seen in mouse and rat beta-cells resulting in part from a difference in Na/Ca exchange activity between these two cells.

AB - In response to glucose, mouse beta-cells display slow oscillations of the membrane potential and cytosolic free Ca2+ concentration ([Ca2+](i))whereas rat beta-cells display a staircase increase in these parameters. Mouse and rat islet cells differ also by their level of Na/Ca exchanger (NCX) activity. The view that the inward current generated by Na/Ca exchange shapes stimulus-induced electrical activity and [Ca2+](i) oscillations in pancreatic beta-cells was examined in insulin-producing BRIN-BD11 cells overexpressing the Na/Ca exchanger BRIN-BD11 cells were stably transfected with NCX1.7, one of the exchanger isoforms identified in the beta-cell. Overexpression could be assessed at the mRNA and protein level. Appropriate targeting to the plasma membrane could be assessed by microfluorescence and the increase in Na/Ca exchange activity. In response to K+, overexpressing cells showed a more rapid increase in [Ca2+](i) on membrane depolarization as well as a more rapid decrease of [Ca2+](i) on membrane repolarization. In response to glucose and tolbutamide, control BRIN cells showed large amplitude [Ca2+](i) oscillations. In, contrast, overexpressing cells showed a staircase increasein[Ca2+](i) without such large oscillations. Diazoxide-induced membrane hyperpolarization restored large amplitude [Ca2+](i) oscillations in overexpressing cells. The present data confirm that Na/Ca exchange plays a significant role in the rat beta-cell [Ca2+](i) homeostasis, the exchanger being a versatile system allowing both Ca2+ entry and outflow. Our data suggest that the current generated by the exchanger shapes stimulus-induced membrane potential and [Ca2+](i) oscillations in insulin-secreting cells, with the difference in electrical activity and [Ca2+](i) behavior seen in mouse and rat beta-cells resulting in part from a difference in Na/Ca exchange activity between these two cells.

M3 - Article

VL - 51

SP - 366

EP - 375

JO - Diabetes

T2 - Diabetes

JF - Diabetes

SN - 0012-1797

IS - 2

ER -