Modulation of Ca(v)3.2 T-type Ca2+ channels by protein kinase C

Jin-Yong Park1, Seong-Woo Jeong, Edward Perez-Reyes

  • 1Department of Life Science, Sogang University, Shinsu-dong, Mapo-Gu, 121-742, Seoul, South Korea.

FEBS Letters
|July 16, 2003
PubMed

Insights

Protein kinase C (PKC) activation by PMA significantly enhances Ca(v)3.2 T-type calcium channel currents. This study clarifies PKC

Area of Science:

  • Molecular biology
  • Neuroscience
  • Ion channel physiology

Background:

  • T-type Ca2+ channels are crucial for various physiological processes.
  • Regulation of T-type Ca2+ channels by protein kinases, particularly protein kinase C (PKC), remains unclear due to conflicting research.
  • Ca(v)3.2 subtype is a key player in neuronal excitability and other functions.

Purpose of the Study:

  • To investigate the specific effects of protein kinase C (PKC) on the activity of Ca(v)3.2 T-type calcium channels.
  • To elucidate the mechanism by which PKC modulates Ca(v)3.2 channel function.
  • To resolve conflicting reports regarding kinase regulation of T-type channels.

Main Methods:

  • Reconstitution of Ca(v)3.2 T-type channels in Xenopus oocytes for electrophysiological studies.
  • Application of phorbol-12-myristate-13-acetate (PMA), a PKC activator, and its inactive stereoisomer (4alpha-PMA).
  • Utilizing PKC inhibitors to confirm the involvement of PKC in the observed effects.

Main Results:

  • Phorbol-12-myristate-13-acetate (PMA) treatment resulted in a substantial, approximately 3-fold, enhancement of Ca(v)3.2 channel current amplitude.
  • The observed augmentation of Ca(v)3.2 currents by PMA was stereospecific, as the inactive isomer 4alpha-PMA did not produce similar effects.
  • Preincubation with specific PKC inhibitors completely abolished the PMA-induced upregulation of Ca(v)3.2 channel activity.

Conclusions:

  • Protein kinase C (PKC) activation by PMA leads to a significant upregulation of Ca(v)3.2 T-type calcium channel activity.
  • These findings provide clear evidence for a direct role of oocyte PKC in enhancing Ca(v)3.2 channel function.
  • This study helps resolve ambiguities in the literature concerning kinase regulation of T-type calcium channels.

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