Enhancement of L-type Ca(2+) current from neonatal mouse ventricular myocytes by constitutively active PKC-betaII. Am J Physiol Cell Physiol 2002 Apr;282(4):C768-74
Date
03/07/2002Pubmed ID
11880265DOI
10.1152/ajpcell.00494.2001Scopus ID
2-s2.0-0036086808 (requires institutional sign-in at Scopus site) 40 CitationsAbstract
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.
Author List
Alden KJ, Goldspink PH, Ruch SW, Buttrick PM, GarcĂa JMESH terms used to index this publication - Major topics in bold
AnimalsAnimals, Newborn
Calcium
Calcium Channels, L-Type
Enzyme Inhibitors
Gene Expression Regulation, Enzymologic
Heart Ventricles
Isoenzymes
Membrane Potentials
Mesylates
Mice
Mice, Transgenic
Muscle Fibers, Skeletal
Myocardium
Protein Kinase C
Protein Kinase C beta
Pyrroles
RNA, Messenger
Reverse Transcriptase Polymerase Chain Reaction
Second Messenger Systems