14734049

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1

Initially during acidosis, Ca transient amplitude (Delta[Ca]i) and the rate constant of [Ca]i decline (k(Ca)) are decreased, but later during acidosis Delta[Ca]i and k(Ca) partially recover. This recovery in rat myocytes could be inhibited by KN-93 suggesting that CaMKII-dependent protein phosphorylation (and enhanced SR Ca uptake) may be responsible. To test whether phospholamban (PLB) is required for the Delta[Ca]i and k(Ca) recovery during acidosis, we used isolated myocytes from PLB knockout (PLB-KO) vs. wild-type (WT) mice. [Ca]i was measured using fluo-3. During the initial phase of acidosis (1-4 min), Delta[Ca]i decreased in WT myocytes (n = 8) from 1.75 +/- 0.19 to 1.10 +/- 0.13 DeltaF/F0 (P < 0.05) and k(Ca) decreased from 3.20 +/- 0.22 to 2.38 +/- 0.18 s(-1) (P < 0.05). Later during acidosis (6-12 min), Delta[Ca]i partially recovered to 1.41 +/- 0.18 DeltaF/F0 and k(Ca) to 2.78 +/- 0.22 s(-1) (i.e. both recovered by approximately 50%). CaMKII inhibition using KN-93 completely prevented this recovery of Delta[Ca]i and k(Ca) during late acidosis in WT myocytes. In PLB-KO myocytes (n = 11) Delta[Ca]i decreased during early acidosis from 2.92 +/- 0.31 to 1.33 +/- 0.17 DeltaF/F0 (P < 0.05) and k(Ca) decreased from 10.45 +/- 0.56 to 7.58 +/- 0.68 s(-1) (P < 0.05). However, Delta[Ca]i did not recover during late acidosis and k(Ca) decreased even more (6.59 +/- 0.65 s(-1)). Parallel results were seen for contractile parameters. We conclude that PLB is crucial to the recovery of Delta[Ca]i and k(Ca) during acidosis. Moreover, PLB phosphorylation by CaMKII plays an important role in limiting the decline in Ca transients (and contraction) during acidosis.

http://linkedlifedata.com/resource/pubmed/commentcorrection/14734049-14734043

eng

IM

MEDLINE

0022-2828

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NLM

67-74

pubmed-meshheading:14734049-Acidosis, pubmed-meshheading:14734049-Animals, pubmed-meshheading:14734049-Benzylamines, pubmed-meshheading:14734049-Calcium, pubmed-meshheading:14734049-Calcium Signaling, pubmed-meshheading:14734049-Calcium-Binding Proteins, pubmed-meshheading:14734049-Calcium-Calmodulin-Dependent Protein Kinase Type 2, pubmed-meshheading:14734049-Calcium-Calmodulin-Dependent Protein Kinases, pubmed-meshheading:14734049-Gene Deletion, pubmed-meshheading:14734049-Guanidines, pubmed-meshheading:14734049-Kinetics, pubmed-meshheading:14734049-Mice, pubmed-meshheading:14734049-Mice, Knockout, pubmed-meshheading:14734049-Myocytes, Cardiac, pubmed-meshheading:14734049-Sarcoplasmic Reticulum, pubmed-meshheading:14734049-Sodium-Hydrogen Antiporter, pubmed-meshheading:14734049-Sulfonamides, pubmed-meshheading:14734049-Sulfones

Phospholamban is required for CaMKII-dependent recovery of Ca transients and SR Ca reuptake during acidosis in cardiac myocytes.

Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't