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Auxiliary beta subunits differentially determine pka utilization of distinct regulatory sites on Cav1.3 L type Ca2+

Yixin Liang1, Steven J Tavalin

  • 1Department of Pharmacology, University of Tennessee Health Science Center, Memphis, Tennessee 38163, USA.

Channels (Austin, Tex.)
|August 12, 2008
PubMed

Insights

The cAMP-dependent protein kinase (PKA) regulates L-type calcium channels (Ca(v)1.3). Auxiliary beta subunits dictate which phosphorylation sites on Ca(v)1.3 are targeted by PKA, influencing channel activity.

Area of Science:

  • Molecular biology
  • Cell physiology
  • Ion channel function

Background:

  • L-type calcium channels (Ca(v)1.1-Ca(v)1.4) are crucial for cellular functions like muscle contraction and hormone secretion.
  • Activity of Ca(v)1.1 and Ca(v)1.2 channels is often modulated by cAMP-dependent protein kinase (PKA) through phosphorylation of the alpha subunit.

Purpose of the Study:

  • To investigate the regulation of Ca(v)1.3 channels by PKA.
  • To identify the specific phosphorylation sites and the role of auxiliary beta subunits in PKA-mediated modulation of Ca(v)1.3 channel activity.

Main Methods:

  • HEK 293 cells were used to study Ca(v)1.3 currents.
  • Introduction of the catalytic subunit of PKA via whole-cell recording.
  • Site-directed mutagenesis of potential PKA phosphorylation sites.
  • Investigation of different auxiliary beta subunits (beta(3) and beta(2a)).

Main Results:

  • PKA selectively enhanced currents carried by the long C-terminal splice variant of Ca(v)1.3 (Ca(v)1.3L) compared to the short variant (Ca(v)1.3S).
  • The persistence of PKA-mediated enhancement was dependent on the auxiliary beta subunit: transient with beta(3) and persistent with beta(2a).
  • Ser1964 and Ser1743 in Ca(v)1.3L were identified as key phosphorylation sites for PKA modulation, with their importance varying based on the beta subunit present.

Conclusions:

  • Auxiliary beta subunits play a critical role in determining the PKA phosphorylation sites on Ca(v)1.3 channels.
  • Beta subunits influence the duration of PKA-mediated channel modulation.
  • These findings suggest that auxiliary beta subunits control the access of signaling enzymes like PKA to L-type calcium channels.

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