Functional coupling between 'R-type' Ca2+ channels and insulin secretion in the insulinoma cell line INS-1.

Among voltage-gated Ca2+ channels the non-dihydropyridine-sensitive alpha1E subunit is functionally less well characterized than the structurally related alpha1A (omega-agatoxin-IVA sensitive, P- /Q-type) and alpha1B (omega-conotoxin-GVIA sensitive, N-type) subunits. In the rat insulinoma cell line, INS-1, a tissue-specific splice variant of alpha1E (alpha1Ee) has been characterized at the mRNA and protein levels, suggesting that INS-1 cells are a suitable model for investigating the function of alpha1Ee. In alpha1E-transfected human embryonic kidney (HEK-293) cells the alpha1E-selective peptide antagonist SNX-482 (100 nM) reduces alpha1Ed- and alpha1Ee-induced Ba2+ inward currents in the absence and presence of the auxiliary subunits beta3 and alpha2delta-2 by more than 80%. The inhibition is fast and only partially reversible. No effect of SNX-482 was detected on the recombinant T-type Ca2+ channel subunits alpha1G, alpha1H, and alpha1I showing that the toxin from the venom of Hysterocrates gigas is useful as an alpha1E-selective antagonist. After blocking known components of Ca2+ channel inward current in INS-1 cells by 2 microM (+/-)-isradipine plus 0.5 microM omega-conotoxin-MVIIC, the remaining current is reduced by 100 nM SNX-482 from -12.4 +/- 1.2 pA/pF to -7.6 +/- 0.5 pA/pF (n = 9). Furthermore, in INS-1 cells, glucose- and KCl-induced insulin release are reduced by SNX-482 in a dose-dependent manner leading to the conclusion that alpha1E, in addition to L-type and non-L-type (alpha1A-mediated) Ca2+ currents, is involved in Ca2+ dependent insulin secretion of INS-1 cells.

[1]  C. Fletcher,et al.  The Status of Voltage-Dependent Calcium Channels in α1E Knock-Out Mice , 2000, The Journal of Neuroscience.

[2]  M. Osanai,et al.  Altered pain responses in mice lacking α1E subunit of the voltage-dependent Ca2+ channel , 2000 .

[3]  N. Klugbauer,et al.  Neuronal distribution and functional characterization of the calcium channel α2δ‐2 subunit , 2000 .

[4]  C. Wollheim,et al.  Beta-cell mitochondria in the regulation of insulin secretion: a new culprit in Type II diabetes , 2000, Diabetologia.

[5]  E. Perez-Reyes Three for T: molecular analysis of the low voltage-activated calcium channel family , 1999, Cellular and Molecular Life Sciences CMLS.

[6]  G. Wang,et al.  An R-Type Ca2+ Current in Neurohypophysial Terminals Preferentially Regulates Oxytocin Secretion , 1999, The Journal of Neuroscience.

[7]  O. Larsson,et al.  Syntaxin 1 interacts with the LD subtype of voltage-gated Ca2+ channels in pancreatic β cells , 1999 .

[8]  B. Adams,et al.  Biphasic, Opposing Modulation of Cloned Neuronal α1E Ca Channels by Distinct Signaling Pathways Coupled to M2 Muscarinic Acetylcholine Receptors , 1999, The Journal of Neuroscience.

[9]  M. Weiergräber,et al.  Immunohistochemical detection of alpha1E voltage-gated Ca(2+) channel isoforms in cerebellum, INS-1 cells, and neuroendocrine cells of the digestive system. , 1999, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[10]  A. Pereverzev,et al.  Isoforms of α1E voltage-gated calcium channels in rat cerebellar granule cells Detection of major calcium channel α1-transcripts by reverse transcription–polymerase chain reaction , 1999, Neuroscience.

[11]  Jung-Ha Lee,et al.  Cloning and Expression of a Novel Member of the Low Voltage-Activated T-Type Calcium Channel Family , 1999, The Journal of Neuroscience.

[12]  Jung-Ha Lee,et al.  Cloning of a novel four repeat protein related to voltage‐gated sodium and calcium channels , 1999, FEBS letters.

[13]  N. Klugbauer,et al.  Molecular Diversity of the Calcium Channel α2δ Subunit , 1999, The Journal of Neuroscience.

[14]  D. Atlas,et al.  The voltage sensitive Lc-type Ca2+ channel is functionally coupled to the exocytotic machinery. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[15]  W. Catterall Structure and function of neuronal Ca2+ channels and their role in neurotransmitter release. , 1998, Cell calcium.

[16]  G. Wang,et al.  Selective peptide antagonist of the class E calcium channel from the venom of the tarantula Hysterocrates gigas. , 1998, Biochemistry.

[17]  H. Grabsch,et al.  New isoform of the neuronal Ca2+ channel α1E subunit in islets of Langerhans and kidney , 1998 .

[18]  E. Perez-Reyes Molecular Characterization of a Novel Family of Low Voltage-Activated, T-Type, Calcium Channels , 1998, Journal of bioenergetics and biomembranes.

[19]  C. Lingle,et al.  Properties of Ba2+ currents arising from human α1E and α1Eβ3 constructs expressed in HEK293 cells: physiology, pharmacology, and comparison to native T-type Ba2+ currents , 1998, Neuropharmacology.

[20]  Y. Zhang,et al.  Cloning and characterization of alpha1H from human heart, a member of the T-type Ca2+ channel gene family. , 1998, Circulation research.

[21]  K. Page,et al.  Identification of the Amino Terminus of Neuronal Ca2+ Channel α1 Subunits α1B and α1E as an Essential Determinant of G-Protein Modulation , 1998, The Journal of Neuroscience.

[22]  R. Tsien,et al.  Antisense oligonucleotides against alpha1E reduce R-type calcium currents in cerebellar granule cells. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[23]  A. E. Boyd,et al.  Class A Calcium Channel Variants in Pancreatic Islets and Their Role in Insulin Secretion* , 1998, The Journal of Biological Chemistry.

[24]  W. Kamphuis,et al.  Expression patterns of voltage-dependent calcium channel α1 subunits (α1A–α1E) mRNA in rat retina , 1998 .

[25]  H. Grabsch,et al.  Structural diversity of the voltage‐dependent Ca2+ channel α1E‐subunit , 1998 .

[26]  Jung-Ha Lee,et al.  Molecular characterization of a neuronal low-voltage-activated T-type calcium channel , 1998, Nature.

[27]  T. Schneider,et al.  Subunit Regulation of the Human Brain α1E Calcium Channel , 1997, The Journal of Membrane Biology.

[28]  A. Bhattacharjee,et al.  T-Type Calcium Channels Facilitate Insulin Secretion by Enhancing General Excitability in the Insulin-Secreting β-Cell Line, INS-1. , 1997, Endocrinology.

[29]  R. Tsien,et al.  Contrasting biophysical and pharmacological properties of T-type and R-type calcium channels , 1997, Neuropharmacology.

[30]  H. Grabsch,et al.  Receptor‐mediated modulation of recombinant neuronal class E calcium channels , 1997, FEBS letters.

[31]  M. Ahlijanian,et al.  L-type calcium channels in insulin-secreting cells: biochemical characterization and phosphorylation in RINm5F cells. , 1997, Molecular Endocrinology.

[32]  D. Pietrobon,et al.  Functional Diversity of P-Type and R-Type Calcium Channels in Rat Cerebellar Neurons , 1996, The Journal of Neuroscience.

[33]  C. Wollheim,et al.  Postreceptor signalling of growth hormone and prolactin and their effects in the differentiated insulin-secreting cell line, INS-1. , 1996, Endocrinology.

[34]  S. Zong,et al.  G-protein modulation of neuronal class E (alpha 1E) calcium channel expressed in GH3 cells. , 1996, Biochemical and biophysical research communications.

[35]  V. Flockerzi,et al.  Gene structure of the murine calcium channel beta3 subunit, cDNA and characterization of alternative splicing and transcription products. , 1996, European journal of biochemistry.

[36]  P. Ince,et al.  The expression of neuronal voltage-dependent calcium channels in human cerebellum. , 1995, Brain research. Molecular brain research.

[37]  T. Snutch,et al.  Biochemical properties and subcellular distribution of the neuronal class E calcium channel alpha 1 subunit , 1995, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[38]  T. Schneider,et al.  Molecular biology of calcium channels. , 1995, Kidney international.

[39]  P. Gilon,et al.  Muscarinic stimulation exerts both stimulatory and inhibitory effects on the concentration of cytoplasmic Ca2+ in the electrically excitable pancreatic B-cell. , 1995, The Biochemical journal.

[40]  T. A. Kinard,et al.  Contribution of L- and non-L-type calcium channels to voltage-gated calcium current and glucose-dependent insulin secretion in HIT-T15 cells. , 1995, Endocrinology.

[41]  G. Yaney,et al.  Unusual carbachol responses in RINm5F cells: evidence for a "distal" site of action in stimulus-secretion coupling. , 1995, Molecular pharmacology.

[42]  J. Costantin,et al.  Molecular analysis and functional expression of the human type E neuronal Ca2+ channel alpha 1 subunit. , 1994, Receptors & channels.

[43]  E. Stefani,et al.  The amino terminus of a calcium channel β subunitsets rates of channel inactivation independently of the subunit's effect on activation , 1994, Neuron.

[44]  L. Philipson,et al.  Structure and functional characterization of neuronal alpha 1E calcium channel subtypes. , 1994, The Journal of biological chemistry.

[45]  L. Forti,et al.  Three novel types of voltage-dependent calcium channels in rat cerebellar neurons , 1994, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[46]  D. Bell,et al.  ω-conotoxin MVIIC reversibly inhibits a human N-type calcium channel and calcium influx into chick synaptosomes , 1994, Neuropharmacology.

[47]  R. Tsien,et al.  Distinctive pharmacology and kinetics of cloned neuronal Ca2+ channels and their possible counterparts in mammalian CNS neurons , 1993, Neuropharmacology.

[48]  S. Vincent,et al.  Structure and functional expression of a member of the low voltage-activated calcium channel family. , 1993, Science.

[49]  C. Wollheim,et al.  Regulation of insulin release by calcium. , 1981, Physiological reviews.

[50]  V. Herbert,et al.  Coated charcoal immunoassay of insulin. , 1965, The Journal of clinical endocrinology and metabolism.

[51]  J. Lang Molecular mechanisms and regulation of insulin exocytosis as a paradigm of endocrine secretion. , 1999, European journal of biochemistry.

[52]  N. Klugbauer,et al.  Voltage-dependent calcium channels: from structure to function. , 1999, Reviews of physiology, biochemistry and pharmacology.

[53]  P. Várnai,et al.  Voltage dependent calcium channels in adrenal glomerulosa cells and in insulin producing cells. , 1998, Cell calcium.

[54]  L. Philipson,et al.  Isoform expression of the voltage-dependent calcium channel alpha 1E. , 1996, Receptors & channels.

[55]  K. Mikoshiba,et al.  Distinctive functional properties of the neuronal BII (class E) calcium channel. , 1994, Receptors & channels.

[56]  C B Wollheim,et al.  Establishment of 2-mercaptoethanol-dependent differentiated insulin-secreting cell lines. , 1992, Endocrinology.

[57]  P. Meda,et al.  Isolation of pancreatic islets and primary culture of the intact microorgans or of dispersed islet cells. , 1990, Methods in enzymology.