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Protein kinase C activation inhibits Cav1.3 calcium channel at NH2-terminal serine 81 phosphorylation site

Ghayath Baroudi1, Yongxia Qu, Omar Ramadan

  • 1Veterans Affairs New York Harbor Healthcare System, Research and Development (151 800 Poly Place, Brooklyn, NY 11209, USA.

American Journal of Physiology. Heart and Circulatory Physiology
|September 16, 2006
PubMed

Insights

Protein kinase C (PKC) modulates Ca(v)1.3 calcium channels via serine 81 phosphorylation. This finding is crucial for understanding neuroendocrine and cardiovascular system functions and developing targeted therapies.

Area of Science:

  • Molecular biology
  • Neuroendocrinology
  • Cardiovascular physiology

Background:

  • Ca(v)1.3 calcium channels are essential for neuroendocrine and cardiovascular functions.
  • Protein kinase C (PKC) is known to regulate ion channel activity.

Purpose of the Study:

  • To elucidate the molecular mechanisms underlying Ca(v)1.3 channel modulation by PKC.
  • To identify specific sites and isozymes involved in this regulation.

Main Methods:

  • Site-directed mutagenesis (Serine 81 to Aspartate).
  • Peptide inhibition assay using an NH(2)-terminal peptide.
  • Investigation of specific PKC isozymes (betaII and epsilon).

Main Results:

  • Phosphorylation at Serine 81 (S81) in the NH(2)-terminal region is critical for PKC-mediated Ca(v)1.3 channel modulation.
  • Mimicking S81 phosphorylation with a negative charge (S81D mutation) replicated PKC effects.
  • A peptide encompassing the S81 site blocked PKC modulation.
  • PKC isozymes betaII and epsilon were identified as key regulators.

Conclusions:

  • Serine 81 is a key phosphorylation site for PKC regulation of Ca(v)1.3 channels.
  • These findings offer insights into Ca(v)1.3 channelopathies and potential therapeutic strategies targeting specific PKC isozymes.

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