Reduction of the same calcium current component by A and C kinases: differential pertussis toxin sensitivity

R A Gross1, R L Macdonald

  • 1Department of Neurology, University of Michigan Medical Center, Ann Arbor 48104-1687.

Insights

Forskolin and 8-Br-cyclic AMP, activators of A kinase, and phorbol 12,13-dibutyrate (PDBu), a C kinase activator, all reduced N-type calcium currents in mouse neurons. C kinase activation required a G protein, unlike A kinase activation.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Cellular Physiology

Background:

  • Voltage-dependent calcium channels are crucial for neuronal function.
  • Cyclic AMP-dependent kinase (A-kinase) and C-kinase play roles in neuronal signaling.
  • Specific calcium current components are differentially regulated.

Purpose of the Study:

  • To investigate the effects of A-kinase and C-kinase activators on distinct calcium current components in mouse dorsal root ganglion neurons.
  • To determine the involvement of G proteins in kinase-mediated modulation of calcium currents.

Main Methods:

  • Voltage-clamp electrophysiology was employed.
  • Mouse dorsal root ganglion neurons in culture were treated with forskolin, 8-Br-cyclic AMP, and phorbol 12,13-dibutyrate (PDBu).
  • Pertussis toxin pretreatment was used to assess G protein involvement.

Main Results:

  • Forskolin and 8-Br-cyclic AMP selectively reduced the transient high-threshold (N-type) calcium current.
  • Phorbol 12,13-dibutyrate (PDBu) also reduced the N-type calcium current.
  • Pertussis toxin blocked PDBu's effect but not the effects of forskolin or 8-Br-cyclic AMP, indicating differential G protein involvement.

Conclusions:

  • Both A-kinase and C-kinase activation selectively inhibit the N-type calcium current in vertebrate neurons.
  • C-kinase-mediated inhibition requires G protein signaling, whereas A-kinase-mediated inhibition does not.
  • These findings elucidate distinct signaling pathways regulating neuronal calcium influx.

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