Neuron
Volume 11, Issue 6, December 1993, Pages 1013-1021
Journal home page for Neuron

Article
Molecular localization of regions in the L-type calcium channel critical for dihydropyridine action

https://doi.org/10.1016/0896-6273(93)90215-DGet rights and content

Abstract

Sensitivity to dihydropyridines (DHPs) is a distinct characteristic that differentiates L-type Ca2+ channels from T-, N-, and P-type Ca2+ channels. To identify regions necessary for the functional effects of DHPs, chimeric Ca2+ channels were constructed in which portions of motif III or motif IV of a DHP-insensitive brain Ca2+ channel, BI-2, were introduced into the DHP-sensitive cardiac L-type Ca2+ channel. The resultant chimeric Ca2+ channels were expressed in Xenopus oocytes, and the effects of a DHP agonist and antagonist were studied. The results show that the linker region between S5 and S6 in motif IV of the L-type Ca2+ channel is a major site for DHP action. The DHP agonist and antagonist molecules interact with distinct sites on the α1 subunit of the L-type Ca2+ channel. The data further show that the SS2–S6 region of motif III is not involved in DHP action but may be an important structural component of inactivation.

References (51)

  • E. Perez-Reyes et al.

    Cloning and expression of a cardiac/brain β subunit of the L-type calcium channel

    J. Biol. Chem.

    (1992)
  • D.F. Slish et al.

    Evidence for the existence of a cardiac specific isoform of the α1 subunit of the voltage-dependent calcium channel

    FEBS Lett.

    (1989)
  • S. Tang et al.

    Molecular localization of ion-selectivity sites within the pore of a human L-type cardiac calcium channel

    J. Biol. Chem.

    (1993)
  • R.W. Tsien et al.

    Molecular diversity of voltage-dependent Ca2+ channels

    Trends Pharmacol. Sci.

    (1991)
  • M.E. Williams et al.

    Structure and functional expression of α1, α2 and β subunits of a novel human neuronal calcium channel subtype

    Neuron

    (1992)
  • P.H. Backx et al.

    Molecular localization of an ion-binding site within the pore of mammalian sodium channels

    Science

    (1992)
  • A.M. Brown et al.

    Dual effects of dihydropyridines on whole cell and unitary calcium currents in single ventricular cells of guinea-pig

    J. Physiol.

    (1986)
  • W.A. Catterall

    Structure and function of voltage-sensitive ion channels

    Science

    (1988)
  • V. Chowdry et al.

    Photoaffinity labeling of biological systems

    Ann. Rev. Biochem.

    (1979)
  • T. Collin et al.

    Molecular cloning of three isoforms of the L-type voltage-dependent calcium channel β subunit from normal human heart

    Circ. Res.

    (1993)
  • G.P. Dube et al.

    Nitrendipine potentiates Bay K 8644-induced contraction of isolated porcine coronary artery: evidence for functionally distinct dihydropyridine receptor subtypes

    Biochem. Biophys. Res. Commun.

    (1985)
  • S.B. Ellis et al.

    Sequence and expression of mRNAs encoding the α1 and α2 subunits of a DHP-sensitive calcium channel

    Science

    (1988)
  • Y. Fujita et al.

    Primary structure and functional expression of the ω-conotoxin-sensitive N-type calcium channel from rabbit brain

    Neuron

    (1993)
  • H. Glossmann et al.

    Calcium channels: introduction into their molecular pharmacology

  • Cited by (0)

    View full text