Regulation of Ca 2+-entry in pancreatic α-cell line by transient receptor potential melastatin 4 plays a vital role in glucagon release

P. L. Nelson, O. Zolochevska, M. L. Figueiredo, A. Soliman, W. H. Hsu, J. M. Feng, H. Zhang, H. Cheng

Research output: Contribution to journalArticle

18 Scopus citations

Abstract

Elevation in the intracellular Ca 2+ concentration stimulates glucagon secretion from pancreatic α-cells. The Transient Receptor Potential Melastatin 4 channel (TRPM4) is critical for Ca 2+ signaling. However, its role in glucagon secreting α-cells has not been investigated. We identified TRPM4 gene expression and protein in the αTC1-6 cell line using RT-PCR and immunocytochemistry. Furthermore, we performed a detailed biophysical characterization of the channel using the patch-clamp technique to confirm that currents typical for TRPM4 were present in αTC1-6 cells. To investigate TRPM4 function, we generated a stable knockdown clone using shRNA and a lentiviral vector. Inhibition of TRPM4 significantly reduced the responses to different agonists during Ca 2+ imaging analysis with Fura-2AM. The reduction in the magnitude of Ca 2+ signals resulted in decreased glucagon secretion. These results suggested that depolarization by TRPM4 may play an important role in controlling glucagon secretion from α-cells and perhaps glucose homeostasis.

Original languageEnglish (US)
Pages (from-to)126-134
Number of pages9
JournalMolecular and Cellular Endocrinology
Volume335
Issue number2
DOIs
StatePublished - Mar 30 2011

Keywords

  • α-Cells
  • Ca signaling
  • Glucagon secretion
  • Pancreas
  • TRPM4

ASJC Scopus subject areas

  • Endocrinology
  • Molecular Biology
  • Biochemistry

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