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1d Subunit Present in Cardiac Muscle
1 Department of Physiology, University of Wisconsin - Madison, Madison, WI, USA
2 Department of Medicine, University of Wisconsin - Madison, Madison, WI, USA
3 Department of Pharmacology, University of Iowa, Iowa City, IA, USA
4 Department of Physiology, University of Wisconsin - Madison, Madison, WI, USA; Department of Medicine, University of Wisconsin - Madison, Madison, WI, USA
* To whom correspondence should be addressed. E-mail: tjk{at}medicine.wisc.edu.
Recent studies have identified a growing diversity of splice variants of auxiliary Ca2+
channel Cav
subunits. The Cav1d isoform encodes a putative protein composed of the aminoterminal half of the full-length Cav1 isoforms and thus lacks the known high affinity binding site recognizing the Ca2+ channel 
1 subunit, the -binding pocket. The present study investigated whether the Cav1d subunit is expressed at the protein level in the heart and if it exhibits any of the functional properties typical of full-length Cav subunits. On Western blots, an antibody directed against the unique carboxyl terminus of Cav1d identified a protein of the predicted MW of 23 kDa from canine and human heart. Immunocytochemistry and surface membrane biotinylation experiments in transfected HEK 293 cells revealed that the full-length Cav1b subunit promoted membrane trafficking of the pore-forming 1C (Cav1.2) subunit to the surface membrane, whereas Cav1d did not. Whole-cell patch clamp analysis of transfected HEK 293 cells demonstrated no effect of co-expression of Cav1d with 1C compared to the 15-fold larger currents and leftward shift in voltage-dependent activation induced by full-length Cav1b co-expression. In contrast, cell attached patch single channel studies demonstrated that coexpression of either Cav1b or Cav1d significantly increased mean open probability 4-5 fold relative to the 1C channels alone, but only Cav1b co-expression increased the number of channels observed per patch. In conclusion, the Cav1d isoforms is expressed in the heart and can modulate the gating of L-type Ca2+ channels, but it does not promote membrane trafficking of the channel complex.
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