کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
10926444 1091845 2008 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Dual regulation of the cardiac L-type calcium channel in L6 cells by protein kinase C
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی بیولوژی سلول
پیش نمایش صفحه اول مقاله
Dual regulation of the cardiac L-type calcium channel in L6 cells by protein kinase C
چکیده انگلیسی
The role of protein kinase C (PKC) in the regulation of cardiac L-type Ca2+ channel activity (LCC) was investigated in L6 rat neonatal myoblasts. Depolarization of fura-2 loaded cells with 140 mM KCl activated a Ba2+ influx pathway that was blocked by nifedipine and stimulated by (−) Bay K 8644. At least two splice variants of the α1C subunit of the cardiac LCC were identified by PCR; the α1S subunit of the skeletal muscle LCC was not detected. Peptides that specifically inhibit translocation of the novel, Ca2+-independent δ and ɛ PKC isozymes reduced Ba2+ influx by 27% and 19%, respectively, whereas a corresponding peptide directed against translocation of classical PKC α had no effect. Ingenol 3,20-dibenzoate, an agent reported to selectively activate novel PKCs, increased Ba2+ uptake by 31% while ethanol, a PKC ɛ agonist, enhanced uptake by 38%. In contrast, selective activation of classical PKCs with thymeleatoxin or an agonist peptide reduced Ba2+ influx by 23-33%. Ba2+ influx was reduced by 30-40% when cells were treated with either a PKC inhibitor (Gö 6983, bisindolylmaleimide) or the PKC activator phorbol-12-myristate-13-acetate. We propose that novel, Ca2+-insensitive PKC(s) enhance cardiac Ca2+ channel activity in L6 cells under basal conditions while activation of the classical, Ca2+-sensitive PKC(s) inhibits channel activity. These findings provide the first evidence that different PKC isozymes exert class-specific opposing effects on cardiac L-type Ca2+ channel activity in L6 myoblasts.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Cell Calcium - Volume 44, Issue 6, December 2008, Pages 545-553
نویسندگان
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