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Front. Endocrinol. | doi: 10.3389/fendo.2018.00040

Calcium channels in postnatal development of rat pancreatic beta cells and their role in insulin secretion

  • 1Cognitive Neuroscience, Universidad Nacional Autónoma de México, Mexico
  • 2Department of Neurobiology, Harvard Medical School, United States

Pancreatic beta cells during the first month of development acquire functional maturity, allowing them to respond to variations in extracellular glucose concentration by secreting insulin. Changes in ionic channel activity are important for this maturation. Within the voltage-gated calcium channels (VGCC), the most studied channels are high-voltage-activated (HVA), principally L-type; while low-voltage-activated (LVA) channels have been poorly studied in native beta cells. We analyzed the changes in the expression and activity of VGCC during the postnatal development in rat beta cells. We observed that the percentage of detection of T-type current increased with the stage of development. T-type calcium current density in adult cells was higher than in neonatal and P20 beta cells. Mean HVA current density also increased with age. Calcium current behavior in P20 beta cells was heterogeneous; almost half of the cells had HVA current densities higher than the adult cells, and this was independent of the presence of T-type current. We detected the presence of α1G, α1H and α1I subunits of LVA channels at all ages. The Cav 3.1 subunit (α1G) was the most expressed. T-type channel blockers mibefradil and TTA-A2 significantly inhibited insulin secretion at 5.6 mM glucose, which suggests a physiological role for T-type channels at basal glucose conditions. Both nifedipine and TTA-A2, drastically decreased the beta cell subpopulation that secretes more insulin, in both basal and stimulating glucose conditions.
We conclude that changes in expression and activity of VGCC during the development play an important role in the physiological maturation of beta cells.

Keywords: LVA and HVA calcium channels, postnatal development, insulin secretion, Reverse hemolytic plaque assay, beta cell maturation

Received: 07 Dec 2017; Accepted: 31 Jan 2018.

Edited by:

Gaetano Santulli, Columbia University, United States

Reviewed by:

Chen Chen, The University of Queensland, Australia
Åke Sjöholm, Division of Endocrinology and Diabetology, Department of Internal Medicine, Gävle Hospital, Sweden  

Copyright: © 2018 Garcia-Delgado, Velasco, Sanchez, Diaz-Garcia and Hiriart. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Marcia Hiriart, Universidad Nacional Autónoma de México, Cognitive Neuroscience, Ciudad Universitaria, Circuito exterior s/n, Delegación Coyoacan, Ciudad de Mexico, 04510, DF, Mexico, mhiriart@ifc.unam.mx