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    J Biol Chem. 2002 Feb 1;277(5):3419-23. Epub 2001 Dec 11.

    A novel long N-terminal isoform of human L-type Ca2+ channel is up-regulated by protein kinase C.

    Blumenstein Y, Kanevsky N, Sahar G, Barzilai R, Ivanina T, Dascal N.

    Department of Physiology and Pharmacology, Sackler School of Medicine, Tel Aviv University, Ramat Aviv 69978, Israel.

    Human L-type voltage-dependent Ca(2+) channels (alpha(1C), or Ca(v)1.2) are up-regulated by protein kinase C (PKC) in native tissues, but in heterologous systems this modulation is absent. In rat and rabbit, alpha(1C) has two N-terminal (NT) isoforms, long and short, with variable initial segments of 46 and 16 amino acids, respectively. The initial 46 amino acids of the long-NT alpha(1C) are crucial for PKC regulation. However, only a short-NT human alpha(1C) is known. We assumed that a long-NT isoform of human alpha(1C) may exist. By homology screening of human genomic DNA, we identified a stretch (termed exon 1a) highly homologous to rabbit long-NT, separated from the next known exon of alpha(1C) (exon 1b, which encodes the alternative, short-NT) by an approximately 80 kb-long intron. The predicted 46-amino acid protein sequence is highly homologous to rabbit long-NT. Reverse transcriptase PCR showed the presence of exon 1a transcript in human cardiac RNA. Expression of human long-NT alpha(1C) in Xenopus oocytes produced Ca(2+) channel enhanced by a PKC activator, whereas the short-NT alpha(1C) was inhibited. The long-NT isoform may be the Ca(2+) channel enhanced by PKC-activating transmitters in human tissues.

    PMID: 11741969 [PubMed - indexed for MEDLINE]

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