Cloning of a T-type Ca2+ channel isoform in insulin-secreting cells.
Open accessAbstract
The T-type Ca2+ channel is an important determinant of electrical activity and of Ca2+ influx in rat and human pancreatic beta-cells. We have identified and sequenced a cDNA encoding a T-type Ca2+ channel alpha1-subunit derived from INS-1, the rat insulin-secreting cell line. The sequence of the cDNA indicates a protein composed of 2,288 amino acids that shares 96.3% identity to alpha1G, the neuronal T-type Ca2+ channel subunit. The transmembrane domains of the protein are highly conserved, but the isoform contains three distinct regions and 10 single amino acid substitutions in other regions. Sequencing rat genomic DNA revealed that the alpha1-subunit we cloned is an alternative splice isoform of alpha1G. By using specific primers and reverse transcription-polymerase chain reaction, we demonstrated that both splice variants are expressed in rat islets. The isoform deduced from INS-1 was also expressed in brain, neonatal heart, and kidney. Functional expression of this alpha1G isoform in Xenopus oocytes generated low voltage-activated Ba2+ currents. These results provide the molecular biological basis for studies of function of T-type Ca2+ channels in beta-cells, which is where these channels may play critical roles in diabetes.
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There is no evidence of low-threshold T-type Ca2+ currents in mouse β-cells, and T-type transcripts are only expressed at very low levels.
“There is no evidence of low-threshold T-type Ca2+ currents in mouse β-cells and T-type transcripts are only expressed at very low levels (although they may be induced following treatment with cytotoxic interleukins (771)).”
From Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men (2018) · cites this paper as [771]
The Discussion (page not provided) says T-type currents have not been observed in primary cultured normal mouse pancreatic β-cells, but reports substantial low-voltage-activated currents in NOD mouse islet cells and NIT-1 cells. The Results discuss T-type transcripts in rat islets and INS-1 cells, not very low transcript levels in mouse β-cells. (LLM, conf=0.86)
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Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men
Rorsman, P., & Ashcroft, F. M. (2018) · Physiological Reviews · doi:10.1152/physrev.00008.2017 · Cited by 793 · see citing works
Central Role of the Adipocyte in the Metabolic Syndrome
Bergman, R. N., Van Citters, G. W., Mittelman, S. D., Dea, M. K., Hamilton-Wessler, M., Kim, S. P., & Ellmerer, M. (2001) · Journal of Investigative Medicine · doi:10.2310/6650.2001.34108 · Cited by 202 · see citing works
- Authors
- Zhuang, H., Bhattacharjee, A., Hu, F., Zhang, M., Goswami, T., Wang, L., Wu, S., Berggren, P. O., & Li, M.
- Affiliations
- University of South Alabama (US)
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 2000-01-01
- Volume
- 49
- Issue
- 1
- Pages
- 59-64
- ISSN
- 0012-1797 (ISSN-L)
- 1939-327X
- OpenAlex
- W2122224574
- Cited by
- 53
- References
- 0
- Citations by year
- 2023: 1 · 2022: 2 · 2021: 3 · 2019: 1 · 2017: 1 · 2015: 1 · 2014: 4
- FWCI
- 1.81
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Diabetes (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (DK-05151)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac electrophysiology and arrhythmias
- Keywords
- T-type calcium channels, alpha1G subunit, insulin-secreting cells, pancreatic beta cells, alternative splicing, splice variants, cDNA cloning, low-voltage-activated calcium current, pancreatic islets
- MeSH terms
- Insulin Secretion, Amino Acid Sequence, Animals, Base Sequence, Cell Line, Cloning, Molecular, Insulin, Islets of Langerhans, Molecular Sequence Data, Rats, Sprague-Dawley, Alternative Splicing, Protein Isoforms, Calcium Channels, T-Type, Rats
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