Determinants of PKC-dependent modulation of a family of neuronal calcium channels

Neuron. 1995 Oct;15(4):929-40. doi: 10.1016/0896-6273(95)90183-3.


The modulation of Ca2+ channel activity by protein kinases contributes to the dynamic regulation of neuronal physiology. Using the transient expression of a family of neuronal Ca2+ channels, we have identified several factors that contribute to the PKC-dependent modulation of Ca2+ channels. First, the nature of the Ca2+ channel alpha 1 subunit protein is critical. Both alpha 1B and alpha 1E channels exhibit a 30%-40% increase in peak currents after exposure to phorbol esters, whereas neither alpha 1A nor alpha 1C channels are significantly affected. This up-regulation can be mimicked for alpha 1E channels by stimulation of a coexpressed metabotropic glutamate receptor (type 1 alpha) through a PKC-dependent pathway. Second, PKC-stimulated up-regulation is dependent upon coexpression with a Ca2+ channel beta subunit. Third, substitution of the cytoplasmic domain I-II linker from alpha 1B confers PKC sensitivity to alpha 1A channels. The results provide direct evidence for the modulation of a subset of neuronal Ca2+ channels by PKC and implicate alpha 1 and beta subunit interactions in regulating channel activity via second messenger pathways.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium / pharmacology
  • Calcium Channels / physiology*
  • Egtazic Acid / analogs & derivatives
  • Egtazic Acid / pharmacology
  • Electric Conductivity
  • Female
  • GTP-Binding Proteins / physiology
  • Indicators and Reagents
  • Kinetics
  • Macromolecular Substances
  • Neurons / physiology*
  • Oocytes / physiology
  • Phorbol 12,13-Dibutyrate / pharmacology
  • Protein Kinase C / metabolism*
  • Receptors, Metabotropic Glutamate / physiology
  • Second Messenger Systems
  • Tetradecanoylphorbol Acetate / pharmacology
  • Virulence Factors, Bordetella / pharmacology
  • Xenopus laevis


  • Calcium Channels
  • Indicators and Reagents
  • Macromolecular Substances
  • Receptors, Metabotropic Glutamate
  • Virulence Factors, Bordetella
  • Phorbol 12,13-Dibutyrate
  • Egtazic Acid
  • Protein Kinase C
  • GTP-Binding Proteins
  • 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid
  • Tetradecanoylphorbol Acetate
  • Calcium