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Calcium channel activation stabilizes a neuronal calcium channel mRNA

Nature Neuroscience volume 2, pages 785–790 (1999)Cite this article

Abstract

We have identified a calcium-dependent pathway in neurons that regulates expression levels of the α1B subunit and N channel current. When neurons are depolarized and voltage-gated calcium channels activated, the half-life of cellular N channel α1B mRNA is prolonged. This stabilizing effect of depolarization is mediated through the 3′ untranslated region of a long form of the α1B mRNA and may represent a form of modulation of N-channel levels that does not require changes in gene transcription. Increases in N channel expression would affect several key neuronal functions controlled by calcium, including transmitter release and neurite outgrowth.

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Figure 1: Forms of α1B message and their decay in vitro (a) Functionally important sites within the 3′ untranslated region of the Ca2+-channel α1B message.
Figure 2: The long form of α1B mRNA was stabilized by depolarization.
Figure 3: Nimodipine inhibits depolarization-induced stabilization of the long form of the α1B mRNA in sympathetic neurons.
Figure 4: Potassium-induced depolarization slows degradation of the long form of α1B mRNA in sympathetic neurons in the presence of Actinomycin D.
Figure 5: Depolarization-induced increases in the N-type Ca2+ channel current density and levels of the α1B subunit in sympathetic neurons maintained in culture.
Figure 6: A comparison of the destabilizing effects of the short and long 3′ untranslated regions on a reporter mRNA in a cell-free degradation assay33.

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Acknowledgements

We thank Terry Snutch and Steve Dubel for providing unpublished partial 3′UTR sequence of rbB-I. We are also grateful to Leslie Tolerico, Justin Fallon and Betsy Quinlin for reading the manuscript. This work was done in partial fulfillment of the requirements for a Ph.D. degree from Brown University (S.S.). Supported by NS 29967 and NS 01927 (D.L.) and Training Grant MH19118.

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Author notes

  1. Zhixin Lin

    Present address: Cold Spring Harbor Laboratory, Beckman Building, 1 Bungtown Rd., Cold Spring Harbor, New York, 11724, USA

Authors and Affiliations

  1. Department of Neuroscience, Brown University, 192 Thayer Street, Box 1953, Providence, 02912, Rhode Island, USA

    Stephanie Schorge, Seema Gupta, Zhixin Lin & Diane Lipscombe

  2. Department of Physiology and Biophysics, Case Western Reserve University School of Medicine, Cleveland, 44106, Ohio, USA

    Maureen W. McEnery

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Correspondence to Diane Lipscombe.

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Schorge, S., Gupta, S., Lin, Z. et al. Calcium channel activation stabilizes a neuronal calcium channel mRNA. Nat Neurosci 2, 785–790 (1999). https://doi.org/10.1038/12153

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