Referenced in: none

Automatically associated channels: TRP , TRPM , TRPM4

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

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

Journal, date & volume: Mol. Cell. Endocrinol., 2011 Mar 30 , 335, 126-34

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/21238535

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.