Unique modulation of L-type Ca2+ channels by short auxiliary β1d subunit present in cardiac muscle

Risa M. Cohen, Jason D. Foell, Ravi C. Balijepalli, Vaibhavi Shah, Johannes W Hell, Timothy J. Kamp

Research output: Contribution to journalArticlepeer-review

33 Scopus citations


Recent studies have identified a growing diversity of splice variants of auxiliary Ca2+ channel Cavβ subunits. The Ca vβ1d isoform encodes a putative protein composed of the amino-terminal half of the full-length Cavβ1 isoform and thus lacks the known high-affinity binding site that recognizes the Ca2+ channel α1-subunit, the α-binding pocket. The present study investigated whether the Cavβ1d subunit is expressed at the protein level in heart, and whether it exhibits any of the functional properties typical of full-length Cavβ subunits. On Western blots, an antibody directed against the unique carboxyl terminus of Cavβ1d identified a protein of the predicted molecular mass of 23 kDa from canine and human hearts. Immunocytochemistry and surface-membrane biotinylation experiments in transfected HEK-293 cells revealed that the full-length Cavβ 1b subunit promoted membrane trafficking of the pore-forming α1C (Cav1.2)-subunit to the surface membrane, whereas the Cavβ1d subunit did not. Whole cell patch-clamp analysis of transfected HEK-293 cells demonstrated no effect of coexpression of the Cavβ1d with the α1C-subunit compared with the 15-fold larger currents and leftward shift in voltage-dependent activation induced by full-length Ca vβ1b coexpression. In contrast, cell-attached patch single-channel studies demonstrated that coexpression of either Ca vβ1b or Cavβ1d significantly increased mean open probability four- to fivefold relative to the α1C-channels alone, but only Cavβ1b coexpression increased the number of channels observed per patch. In conclusion, the Cavβ1d isoform is expressed in heart and can modulate the gating of L-type Ca2+ channels, but it does not promote membrane trafficking of the channel complex.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Issue number5 57-5
StatePublished - May 2005
Externally publishedYes


  • Electrophysiology
  • Heart
  • Ion
  • Splice variant

ASJC Scopus subject areas

  • Physiology


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