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Effect of Ca(v)beta subunits on structural organization of Ca(v)1.2 calcium channels

Evgeny Kobrinsky1, Parwiz Abrahimi, Son Q Duong

  • 1National Institute on Aging, National Institutes of Health, Baltimore, Maryland, United States of America.

Plos One
|June 4, 2009
PubMed
Abstract

Insights

The type of Ca(v)beta subunit significantly influences the clustering and proximity of Ca(v)1.2 calcium channels in live cell plasma membranes. Different Ca(v)beta subunits alter the structural organization of these crucial signaling channels.

Area of Science:

  • Cellular and Molecular Biology
  • Biophysics
  • Cardiovascular Physiology

Background:

  • Voltage-gated calcium channels, specifically Ca(v)1.2, are vital for cellular calcium signaling.
  • The pore-forming alpha(1C) subunit of Ca(v)1.2 channels is modulated by accessory Ca(v)beta subunits.
  • Four Ca(v)beta subunit genes (Ca(v)beta(1)-beta(4)) encode proteins with tissue-specific expression patterns.

Purpose of the Study:

  • To investigate how different Ca(v)beta subunits (beta(1b), beta(2d), beta(3)) affect the plasma membrane structure of Ca(v)1.2 channels in live cells.
  • To determine the impact of Ca(v)beta subunits on Ca(v)1.2 channel clustering and subunit proximity.

Main Methods:

  • Total internal reflection fluorescence microscopy (TIR-FM) to visualize Ca(v)1.2 clustering.
  • Three-color Förster resonance energy transfer (FRET) microscopy to measure inter- and intramolecular distances.
  • Live-cell imaging techniques to study channel organization in the plasma membrane.

Main Results:

  • Ca(v)1.2 channel clustering in the plasma membrane is dependent on the specific Ca(v)beta subunit present.
  • Ca(v)beta(1b) resulted in the highest density and smallest size of Ca(v)1.2 clusters.
  • Ca(v)beta(3) led to fewer, larger Ca(v)1.2 clusters, with altered inter-subunit distances.
  • Ca(v)beta type significantly affects the distance between neighboring alpha(1C) subunits, but not intramolecular distances.

Conclusions:

  • The structural organization of Ca(v)1.2 channels within the plasma membrane is dictated by the type of associated Ca(v)beta subunit.
  • Ca(v)beta subunits play a critical role in modulating the spatial arrangement and proximity of Ca(v)1.2 channels.

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