Antisense Depletion of Beta-subunits Modulates the Biophysical and Pharmacological Properties of Neuronal Calcium Channels

Overview

Journal J Physiol

Specialty Physiology

Date 1995 Feb 1

PMID 7537818

Citations 41

Authors

N S Berrow

V Campbell

E M Fitzgerald

K Brickley

A C Dolphin

Affiliations

Soon will be listed here.

Abstract

1. The role of the voltage-dependent calcium channel (VDCC) beta-subunit has been examined in cultured rat dorsal root ganglion neurones (DRGs). An antipeptide antibody was raised and this recognized proteins corresponding to beta-subunits in a number of preparations. Immunoreactivity for the VDCC beta-subunit in DRGs was concentrated on the internal side of the plasma membrane but was also present in the cytoplasm. 2. A twenty-six-mer antisense oligonucleotide with homology to all published VDCC beta-subunit sequences was microinjected into individual cells, and maximal depletion of VDCC beta-subunit immunoreactivity was observed after 108 h suggesting a half-life for the turnover of the beta-subunit greater than 50 h. No depletion was obtained with nonsense oligonucleotide. 3. The effect of depletion of VDCC beta-subunit immunoreactivity on calcium channel currents in these cells was a reduction in amplitude of the maximum current of about 47%, and a shift in the voltage dependence of current activation of about +7 mV. These effects are the converse of those observed following co-expression of cloned beta- with alpha 1-subunits in oocytes and other expression systems. 4. The ability of the 1,4-dihydropyridine (DHP) agonist Bay K 8644 to enhance calcium channel currents was greatly reduced following depletion of beta-subunit immunoreactivity. This result is in agreement with the finding in several systems that co-expression of the beta-subunit with alpha 1-subunits results in an increased number of DHP binding sites. 5. These results show that calcium channel beta-subunits form part of native neuronal calcium channels and modify their biophysical and pharmacological properties.

Citing Articles

The Interplay Between Splicing of Two Exon Combinations Differentially Affects Membrane Targeting and Function of Human Ca2.2.

Dahimene S, Page K, Nieto-Rostro M, Pratt W, Dolphin A Function (Oxf). 2023; 5(1):zqad060.

PMID: 38020068 PMC: 10666670. DOI: 10.1093/function/zqad060.

Mechanisms controlling the trafficking, localization, and abundance of presynaptic Ca channels.

Cunningham K, Littleton J Front Mol Neurosci. 2023; 15:1116729.

PMID: 36710932 PMC: 9880069. DOI: 10.3389/fnmol.2022.1116729.

Role of High Voltage-Gated Ca Channel Subunits in Pancreatic β-Cell Insulin Release. From Structure to Function.

Tuluc P, Theiner T, Jacobo-Piqueras N, Geisler S Cells. 2021; 10(8).

PMID: 34440773 PMC: 8393260. DOI: 10.3390/cells10082004.

How Postdoctoral Research in Paul Greengard's Laboratory Shaped My Scientific Career, Although I Never Did Another Phosphorylation Assay.

Dolphin A J Neurosci. 2021; 41(10):2070-2075.

PMID: 33558431 PMC: 8018760. DOI: 10.1523/JNEUROSCI.3002-20.2021.

Trafficking of neuronal calcium channels.

Weiss N, Zamponi G Neuronal Signal. 2020; 1(1):NS20160003.

PMID: 32714572 PMC: 7373241. DOI: 10.1042/NS20160003.

References

Neely A, Wei X, Olcese R, Birnbaumer L, Stefani E . Potentiation by the beta subunit of the ratio of the ionic current to the charge movement in the cardiac calcium channel. Science. 1993; 262(5133):575-8. DOI: 10.1126/science.8211185. View

De Jongh K, Warner C, Catterall W . Subunits of purified calcium channels. Alpha 2 and delta are encoded by the same gene. J Biol Chem. 1990; 265(25):14738-41. View

Zhang J, Randall A, Ellinor P, Horne W, Sather W, Tanabe T . Distinctive pharmacology and kinetics of cloned neuronal Ca2+ channels and their possible counterparts in mammalian CNS neurons. Neuropharmacology. 1993; 32(11):1075-88. DOI: 10.1016/0028-3908(93)90003-l. View

Williams M, Brust P, FELDMAN D, Patthi S, Simerson S, Maroufi A . Structure and functional expression of an omega-conotoxin-sensitive human N-type calcium channel. Science. 1992; 257(5068):389-95. DOI: 10.1126/science.1321501. View

Snutch T, Reiner P . Ca2+ channels: diversity of form and function. Curr Opin Neurobiol. 1992; 2(3):247-53. DOI: 10.1016/0959-4388(92)90111-w. View

Leonetti J, Mechti N, Degols G, Gagnor C, Lebleu B . Intracellular distribution of microinjected antisense oligonucleotides. Proc Natl Acad Sci U S A. 1991; 88(7):2702-6. PMC: 51306. DOI: 10.1073/pnas.88.7.2702. View

Ahlijanian M, Westenbroek R, Catterall W . Subunit structure and localization of dihydropyridine-sensitive calcium channels in mammalian brain, spinal cord, and retina. Neuron. 1990; 4(6):819-32. DOI: 10.1016/0896-6273(90)90135-3. View

McEnery M, Snowman A, Snyder S . Evidence for subtypes of the omega-conotoxin GVIA receptor. Identification of the properties intrinsic to the high-affinity receptor. Ann N Y Acad Sci. 1991; 635:435-7. DOI: 10.1111/j.1749-6632.1991.tb36519.x. View

Castellano A, Wei X, Birnbaumer L, Perez-Reyes E . Cloning and expression of a third calcium channel beta subunit. J Biol Chem. 1993; 268(5):3450-5. View

10.

Kleuss C, Hescheler J, Ewel C, Rosenthal W, Schultz G, Wittig B . Assignment of G-protein subtypes to specific receptors inducing inhibition of calcium currents. Nature. 1991; 353(6339):43-8. DOI: 10.1038/353043a0. View

11.

Third J . SOME CLINICAL OBSERVATIONS ON ARTERIO-SCLEROSIS. Can Med Assoc J. 2010; 3(4):261-8. PMC: 1579729. View

12.

Stea A, DUBEL S, Pragnell M, Leonard J, Campbell K, Snutch T . A beta-subunit normalizes the electrophysiological properties of a cloned N-type Ca2+ channel alpha 1-subunit. Neuropharmacology. 1993; 32(11):1103-16. DOI: 10.1016/0028-3908(93)90005-n. View

13.

Hui A, Ellinor P, Krizanova O, Wang J, Diebold R, Schwartz A . Molecular cloning of multiple subtypes of a novel rat brain isoform of the alpha 1 subunit of the voltage-dependent calcium channel. Neuron. 1991; 7(1):35-44. DOI: 10.1016/0896-6273(91)90072-8. View

14.

Pragnell M, Sakamoto J, Jay S, Campbell K . Cloning and tissue-specific expression of the brain calcium channel beta-subunit. FEBS Lett. 1991; 291(2):253-8. DOI: 10.1016/0014-5793(91)81296-k. View

15.

Castellano A, Wei X, Birnbaumer L, Perez-Reyes E . Cloning and expression of a neuronal calcium channel beta subunit. J Biol Chem. 1993; 268(17):12359-66. View

16.

Campbell V, Berrow N, Dolphin A . GABAB receptor modulation of Ca2+ currents in rat sensory neurones by the G protein G(0): antisense oligonucleotide studies. J Physiol. 1993; 470:1-11. PMC: 1143901. DOI: 10.1113/jphysiol.1993.sp019842. View

17.

Ruth P, Rohrkasten A, Biel M, Bosse E, Regulla S, Meyer H . Primary structure of the beta subunit of the DHP-sensitive calcium channel from skeletal muscle. Science. 1989; 245(4922):1115-8. DOI: 10.1126/science.2549640. View

18.

Perez-Reyes E, Castellano A, Kim H, Bertrand P, Baggstrom E, Lacerda A . Cloning and expression of a cardiac/brain beta subunit of the L-type calcium channel. J Biol Chem. 1992; 267(3):1792-7. View

19.

Mintz I, Adams M, Bean B . P-type calcium channels in rat central and peripheral neurons. Neuron. 1992; 9(1):85-95. DOI: 10.1016/0896-6273(92)90223-z. View

20.

Lledo P, Vernier P, Vincent J, Mason W, Zorec R . Inhibition of Rab3B expression attenuates Ca(2+)-dependent exocytosis in rat anterior pituitary cells. Nature. 1993; 364(6437):540-4. DOI: 10.1038/364540a0. View