Enhancement of L-type Ca(2+) current from neonatal mouse ventricular myocytes by constitutively active PKC-betaII

The cardiacL-type calcium current (I_Ca) can be modified byactivation of protein kinase C (PKC). However, the effect of PKC activation on I_Ca is still controversial. Somestudies have shown a decrease in current, whereas other studies havereported a biphasic effect (an increase followed by a decrease incurrent or vice versa). A possible explanation for the conflictingresults is that several isoforms of PKC with opposing effects onI_Ca were activated simultaneously. Here, weexamined the influence of a single PKC isoform (PKC-II) on L-typecalcium channels in isolation from other cardiac isoforms, using atransgenic mouse that conditionally expresses PKC-II. Ventricularcardiac myocytes were isolated from newborn mice and examined forexpression of the transgene using single cell RT-PCR afterI_Ca recording. Cells expressing PKC-II showeda twofold increase in nifedipine-sensitive I_Ca. The PKC-II antagonist LY-379196 returned I_Caamplitude to levels found in non-PKC-II-expressing myocytes. Theincrease in I_Ca was independent ofCa_v1.2-subunit mRNA levels as determined by quantitativeRT-PCR. Thus these data demonstrate that PKC- is a potent modulatorof cardiac L-type calcium channels and that this specific isoformincreases I_Ca in neonatal ventricular myocytes.