Branding/Logomark minus Citation Combined Shape Icon/Bookmark-empty Icon/Copy Icon/Collection Icon/Close Copy 7 no author result Created with Sketch. Icon/Back Created with Sketch. Match!

Cloning of a T-type Ca2+ channel isoform in insulin-secreting cells.

Published on Jan 1, 2000in Diabetes 7.20
· DOI :10.2337/diabetes.49.1.59
Hean Zhuang4
Estimated H-index: 4
,
Arin Bhattacharjee22
Estimated H-index: 22
+ 6 AuthorsMing Li23
Estimated H-index: 23
Cite
Abstract
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.
  • References (9)
  • Citations (42)
Cite
References9
Newest
Published on Feb 1, 1998in Nature 43.07
Edward Perez-Reyes57
Estimated H-index: 57
(Loyola University Medical Center),
Leanne L. Cribbs33
Estimated H-index: 33
(Loyola University Medical Center)
+ 6 AuthorsJung-Ha Lee9
Estimated H-index: 9
(Loyola University Medical Center)
The molecular diversity of voltage-activated calcium channels was established by studies showing that channels could be distinguished by their voltage-dependence, deactivation and single-channel conductance1,2,3. Low-voltage-activated channels are called ‘T’ type because their currents are both transient (owing to fast inactivation) and tiny (owing to small conductance)2. T-type channels are thought to be involved in pacemaker activity, low-threshold calcium spikes, neuronal oscillations and res...
629 Citations Source Cite
Published on Sep 1, 1997in Endocrinology 3.80
Arin Bhattacharjee22
Estimated H-index: 22
(USA: University of South Alabama),
Richard M Whitehurst6
Estimated H-index: 6
(USA: University of South Alabama)
+ 2 AuthorsMing Li23
Estimated H-index: 23
(USA: University of South Alabama)
The present study addresses the function of T-type voltage-gated calcium channels in insulin-secreting cells. We used whole-cell voltage and current recordings, capacitance measurements, and RIA techniques to determine the contribution of T-type calcium channels in modulation of electrical activity and in stimulus-secretion coupling in a rat insulin secreting cell line, INS-1. By employing a double pulse protocol in the current-clamp mode, we found that activation of T-type calcium channels prov...
60 Citations Source Cite
Published on Nov 1, 1994in Metabolism-clinical and Experimental 6.51
Seika Kato14
Estimated H-index: 14
(Kyoto University),
Hitoshi Ishida30
Estimated H-index: 30
(Kyoto University)
+ 5 AuthorsYutaka Seino24
Estimated H-index: 24
(Kyoto University)
Abstract Using a whole-cell patch-clamp technique, voltage-dependent Ca 2+ -channel activities were found to be increased in cultured single β cells isolated from neonatally streptozocin-induced diabetic rats (NSZ rats). The current-voltage relationship and inactivation time course of Ba 2+ currents via L-type Ca 2+ channels were indistinguishable between NSZ and control rats. However, the current density observed in NSZ rats was significantly greater than that in control rats. Ba 2+ currents vi...
11 Citations Source Cite
Published on Nov 1, 1992in American Journal of Physiology-cell Physiology 3.55
Bruce A. Biagi10
Estimated H-index: 10
,
Boris Mlinar8
Estimated H-index: 8
,
John J. Enyeart25
Estimated H-index: 25
The whole cell version of the patch-clamp technique was used to identify and characterize voltage-gated Ca2+, Na+, and K+ currents in the calcitonin-secreting human thyroid TT cell line. Ca2+ current consisted of a single low-voltage-activated rapidly inactivating component. The current was one-half maximally activated at a potential of -27 mV, while steady-state voltage-dependent inactivation was one-half complete at -51 mV. The Ca2+ current inactivated with a voltage-dependent time constant th...
11 Citations Source Cite
Published on Sep 27, 1991in Science 41.04
William A. Catterall134
Estimated H-index: 134
(UW: University of Washington)
131 Citations Source Cite
Published on Aug 1, 1990in Biophysical Journal 3.67
S. Sala1
Estimated H-index: 1
(UMB: University of Maryland, Baltimore),
D.R. Matteson2
Estimated H-index: 2
(UMB: University of Maryland, Baltimore)
Using the cell-attached configuration of the patch clamp technique, we have identified two different types of Ca channels in rat pancreatic beta-cell membranes. The two channels differ in single channel conductance, voltage dependence, and inactivation properties. The single-channel conductance, measured with 100 mM Ba2+ in the pipette, was 21.8 pS for the large channel and 6.4 pS for the small channel. The large-conductance channel is similar to the fast deactivating or L-type Ca channel descri...
31 Citations Source Cite
Published on Nov 1, 1989in Nature 43.07
Paul A. Smith27
Estimated H-index: 27
(University of Oxford),
Patrik Rorsman55
Estimated H-index: 55
(University of Oxford),
Frances M. Ashcroft83
Estimated H-index: 83
(University of Oxford)
GLUCOSE stimulates insulin secretion from the pancreatic β-cell by increasing the cytosolic calcium concentration1. It is believed that this increment results mainly from Ca2+ influx through dihydropyridine-sensitive calcium channels because insulin secretion is abolished by dihydropyridine antagonists2 and is potentiated by dihydropyridine agonists3. Glucose may influence Ca2+ influx through these channels in two ways: either by regulating the β-cell membrane potential or by biochemical modulat...
118 Citations Source Cite
Published on Jan 1, 1989in Progress in Biophysics & Molecular Biology 2.70
Frances M. Ashcroft83
Estimated H-index: 83
(University of Oxford),
Patrik Rorsman51
Estimated H-index: 51
(University of Gothenburg)
914 Citations Source Cite
Published on May 1, 1988in The Journal of General Physiology 4.26
Marcia Hiriart21
Estimated H-index: 21
,
D. R. Matteson1
Estimated H-index: 1
The reverse hemolytic plaque assay (RHPA) was used to study the secretory properties of single rat pancreatic B cells, and to identify insulin-secreting cells for patch-clamp experiments. In secretion studies using the RHPA, we find that the percentage of secreting B cells and the amount of insulin secreted per B cell increase as the glucose concentration is raised from 0 to 20 mM. Using the whole-cell variation of the patch-clamp technique, we find that identified B cells have three types of ch...
149 Citations Source Cite
Cited By42
Newest
Published on Jan 1, 2018in Physiological Reviews 24.25
Patrik Rorsman55
Estimated H-index: 55
(University of Oxford),
Frances M. Ashcroft83
Estimated H-index: 83
(University of Oxford)
The pancreatic β-cell plays a key role in glucose homeostasis by secreting insulin, the only hormone capable of lowering the blood glucose concentration. Impaired insulin secretion results in the chronic hyperglycemia that characterizes type 2 diabetes (T2DM), which currently afflicts >450 million people worldwide. The healthy β-cell acts as a glucose sensor matching its output to the circulating glucose concentration. It does so via metabolically induced changes in electrical activity, which cu...
38 Citations Source Cite
Published on Oct 1, 2015in Biochemical Journal 4.33
Akos A. Gerencser24
Estimated H-index: 24
(Touro University California),
Hindrik Mulder48
Estimated H-index: 48
(Lund University),
David G. Nicholls82
Estimated H-index: 82
(Lund University)
In the presence of high glucose or pyruvate, INS-1 832/13 insulinoma cells undergo stochastic oscillations in plasma membrane potential (Δψ p ) leading to associated fluctuations in cytosolic free Ca 2+ concentration ([Ca 2+ ] c ). Oscillations are not driven by upstream metabolic fluctuations, but rather by autonomous ionic mechanisms, the details of which are unclear. We have investigated the nature of the oscillator, with simultaneous fluorescence monitoring of Δψ p , [Ca 2+ ] c and exocytosi...
7 Citations Source Cite
Published on Jan 1, 2015
Ming Li (Tulane University)
Increases in plasma glucose concentration enhance the expression and activity of T-type Ca2+ channels in insulin-secreting pancreatic β-cells. The resulting elevation in T-type Ca2+ channel activity results in an elevation in the basal [Ca2+]i of β-cells. High [Ca2+]i in turn causes the internalization of L-type Ca2+ channels from cytoplasmic membrane, which contributes to glucose toxicity in β-cells. Increased activity of T-type Ca2+ channels, along with elevated [Ca2+]i, promotes low threshold...
Source Cite
Published on Jan 1, 2015
Jonathan E. Pottle3
Estimated H-index: 3
(Tulane University),
Lloyd S. Gray20
Estimated H-index: 20
Calcium signaling plays an important role in the regulation of cell cycling. Cells passing from G1 to S require both extracellular calcium and functional plasma membrane calcium channels in order to activate various downstream enzymes, such as ribonucleotide reductase, thymidine kinase, thymidylate synthase, and DNA polymerase. Fast proliferating cancer cells contain higher levels of basal [Ca2+]i than normal epithelial cells. Indeed, in order to compensate for the increased requirement for Ca2+...
Source Cite
Published on Oct 1, 2014in American Journal of Physiology-cell Physiology 3.55
Hassan Sellak3
Estimated H-index: 3
(Georgia Regents University),
Chun Zhou9
Estimated H-index: 9
(USA: University of South Alabama)
+ 3 AuthorsSongwei Wu1
Estimated H-index: 1
(Georgia Regents University)
The low-voltage-activated T-type Ca2+ channels play an important role in mediating the cellular responses to altered oxygen tension. Among three T-type channel isoforms, α1G, α1H, and α1I, only α1H was found to be upregulated under hypoxia. However, mechanisms underlying such hypoxia-dependent isoform-specific gene regulation remain incompletely understood. We, therefore, studied the hypoxia-dependent transcriptional regulation of α1G and α1H gene promoters with the aim to identify the functiona...
4 Citations Source Cite
Published on Mar 18, 2014in Frontiers in Behavioral Neuroscience 2.62
Giuseppe Gangarossa7
Estimated H-index: 7
(French Institute of Health and Medical Research),
Sophie Laffray7
Estimated H-index: 7
+ 1 AuthorsEmmanuel Valjent38
Estimated H-index: 38
(French Institute of Health and Medical Research)
The fine-tuning of neuronal excitability relies on a tight control of Ca2+ homeostasis. The low voltage-activated T-type calcium channels (Cav3.1, Cav3.2 and Cav3.3 isoforms) play a critical role in regulating these processes. Despite their wide expression throughout the central nervous system, the implication of T-type Cav3.2 isoform in brain functions is still poorly characterized. Here we investigate the effect of genetic ablation of this isoform in affective disorders, including anxiety, cog...
33 Citations Source Cite
Published on Feb 1, 2012in Journal of Pharmacology and Experimental Therapeutics 3.62
Viktor Yarotskyy7
Estimated H-index: 7
,
Keith S. Elmslie24
Estimated H-index: 24
T-type calcium channels (CaV3) play an important role in many physiological and pathological processes, including cancerogenesis. CaV3 channel blockers have been proposed as potential cancer treatments. Roscovitine, a trisubstituted purine, is a cyclin-dependent kinase (CDK) inhibitor that is currently undergoing phase II clinical trials as an anticancer drug and has been shown to affect calcium and potassium channel activity. Here, we investigate the effect of roscovitine on CaV3.1 channels. Ca...
6 Citations Source Cite
Published on May 1, 2010in Pancreas 2.67
Changqin Liu9
Estimated H-index: 9
,
Xuejun Li13
Estimated H-index: 13
+ 3 AuthorsShuyu Yang15
Estimated H-index: 15
Source Cite
Manuel Navarro-Gonzalez3
Estimated H-index: 3
(ANU: Australian National University),
Thomas Grayson6
Estimated H-index: 6
(ANU: Australian National University)
+ 2 AuthorsCaryl E. Hill36
Estimated H-index: 36
(ANU: Australian National University)
SUMMARY 1 Constriction of cerebral arteries is considered to depend on L-type voltage-dependent calcium channels (VDCCs); however, many previous studies have used antagonists with potential non-selective actions. Our aim was to determine the expression and function of VDCCs in the rat basilar artery. 2 The relative expression of VDCC subtypes was assessed using quantitative polymerase chain reaction and immunohistochemistry. Data were correlated with physiological studies of vascular function. D...
29 Citations Source Cite
Marcia Hiriart21
Estimated H-index: 21
(UNAM: National Autonomous University of Mexico),
Lydia Aguilar-Bryan43
Estimated H-index: 43
(Pacific Northwest Diabetes Research Institute)
Mammalian β-cells are acutely and chronically regulated by sensing surrounding glucose levels that determine the rate at which insulin is secreted, to maintain euglycemia. Experimental research in vitro and in vivo has shown that, when these cells are exposed to adverse conditions like long periods of hypoglycemia or hyperglycemia, their capability to sense glucose is decreased. Understanding the normal physiology and identifying the main players along this route becomes paramount. In this revie...
62 Citations Source Cite