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 language | English (US) |
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Pages (from-to) | 126-134 |
Number of pages | 9 |
Journal | Molecular and Cellular Endocrinology |
Volume | 335 |
Issue number | 2 |
DOIs | |
State | Published - Mar 30 2011 |
Externally published | Yes |
Keywords
- α-Cells
- Ca signaling
- Glucagon secretion
- Pancreas
- TRPM4
ASJC Scopus subject areas
- Endocrinology
- Molecular Biology
- Biochemistry