Faculty Collaboration Database

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

03/07/2002

Pubmed ID

11880265

DOI

10.1152/ajpcell.00494.2001

Scopus ID

2-s2.0-0036086808 (requires institutional sign-in at Scopus site)   41 Citations

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.

Author List

Alden KJ, Goldspink PH, Ruch SW, Buttrick PM, García J

MESH terms used to index this publication - Major topics in bold

Animals
Animals, 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