title: Enhancement of L-type Ca(2+) current from neonatal mouse ventricular myocytes by constitutively active PKC-betaII.
abstract: The cardiac L-type calcium current (I(Ca)) can be modified by activation of protein kinase C (PKC). However, the effect of PKC activation on I(Ca) is still controversial. Some studies have shown a decrease in current, whereas other studies have reported a biphasic effect (an increase followed by a decrease in current or vice versa). A possible explanation for the conflicting results is that several isoforms of PKC with opposing effects on I(Ca) were activated simultaneously. Here, we examined the influence of a single PKC isoform (PKC-betaII) on L-type calcium channels in isolation from other cardiac isoforms, using a transgenic mouse that conditionally expresses PKC-betaII. Ventricular cardiac myocytes were isolated from newborn mice and examined for expression of the transgene using single cell RT-PCR after I(Ca) recording. Cells expressing PKC-betaII showed a twofold increase in nifedipine-sensitive I(Ca). The PKC-betaII antagonist LY-379196 returned I(Ca) amplitude to levels found in non-PKC-betaII-expressing myocytes. The increase in I(Ca) was independent of Ca(v)1.2-subunit mRNA levels as determined by quantitative RT-PCR. Thus these data demonstrate that PKC-beta is a potent modulator of cardiac L-type calcium channels and that this specific isoform increases I(Ca) in neonatal ventricular myocytes.
authors.affiliation: Department of Physiology and Biophysics, Department of Medicine, College of Medicine, University of Illinois at Chicago, 900 S. Ashland Ave., Chicago, IL 60607, USA.
authors.forename: Kris J
authors.initials: KJ
authors.lastname: Alden
authors.forename: Paul H
authors.initials: PH
authors.lastname: Goldspink
authors.forename: Stuart W
authors.initials: SW
authors.lastname: Ruch
authors.forename: Peter M
authors.initials: PM
authors.lastname: Buttrick
authors.forename: Jesús
authors.initials: J
authors.lastname: García
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002118:Calcium / Q000378:metabolism; D020746:Calcium Channels, L-Type / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology; D006352:Heart Ventricles / Q000166:cytology / Q000201:enzymology; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism*; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D008698:Mesylates / Q000494:pharmacology; D051379:Mice; D008822:Mice, Transgenic; D018485:Muscle Fibers, Skeletal / Q000201:enzymology*; D009206:Myocardium / Q000166:cytology* / Q000201:enzymology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism*; D064546:Protein Kinase C beta; D011758:Pyrroles / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015290:Second Messenger Systems / Q000502:physiology
chemical_list: C434605:5,21 - 12,17-dimetheneo-18H-dibenzo(i,o)pyrrolo(3,4-1)(1,8)diazacyclohexandecine-18,10(19H)dione,8((dimethylamino)methyl)-6,7,8,9,10,11-hexahydro,monomethanesulfonate; D020746:Calcium Channels, L-Type; D004791:Enzyme Inhibitors; D007527:Isoenzymes; D008698:Mesylates; D011758:Pyrroles; D012333:RNA, Messenger; D011493:Protein Kinase C; D064546:Protein Kinase C beta; D002118:Calcium