Modulation of muscle contraction by a cell-permeable peptide.
In contrast to immortal cell lines, primary cells are hardly susceptible to intracellular delivery methods such as transfection. In this study, we evaluated the direct delivery of several cell-permeable peptides under noninvasive conditions into living primary adult rat cardiomyocytes. We specifically monitored the functional effects of a cell-permeable peptide containing the 15 amino acid N-terminal peptide from human ventricular light chain-1 (VLC-1) on contraction and intracellular Ca2+ signals after electrical stimulation in primary adult cardiomyocytes. The transducible VLC-1 variant was taken up by cardiomyocytes within 5 min with more than 95% efficiency and localized to sarcomeric structures. Analysis of the functional effects of the cell-permeable VLC-1 revealed an enhancement of the intrinsic contractility of cardiomyocytes without affecting the intracellular Ca2+. Therefore, peptide transduction mediated by cell-penetrating peptides represents not only a unique strategy to enhance heart muscle function with no secondary effect on intracellular Ca2+ but also an invaluable tool for the modulation and manipulation of protein interactions in general and in primary cells.
Tünnemann
Gisela
G
Max Delbrück Center for Molecular Medicine, Robert Rössle Str. 10, 13125, Berlin, Germany.
Karczewski
Peter
P
Haase
Hannelore
H
Cardoso
M Cristina
MC
Morano
Ingo
I
D000818:Animals; D020013:Calcium Signaling / Q000187:drug effects*; D002316:Cardiotonic Agents / Q000378:metabolism / Q000494:pharmacology*; D002463:Cell Membrane Permeability; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D006801:Humans; D018613:Microscopy, Confocal; D009200:Myocardial Contraction / Q000187:drug effects*; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism; D018994:Myosin Light Chains / Q000378:metabolism / Q000494:pharmacology*; D010446:Peptide Fragments / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D011921:Rats, Inbred WKY; D012518:Sarcomeres / Q000187:drug effects / Q000378:metabolism; D024723:Ventricular Myosins / Q000378:metabolism / Q000494:pharmacology*
D002316:Cardiotonic Agents; D018994:Myosin Light Chains; D010446:Peptide Fragments; C076659:myosin light chain I; D024723:Ventricular Myosins
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