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Ca 2+ channel remodeling in perfused heart: effects of mechanical work and interventions affecting Ca 2+ cycling on sarcolemmal and sarcoplasmic reticulum Ca 2+ channels
Author(s) -
Zucchi Riccardo,
Ghelardoni Sandra,
Carnicelli Vittoria,
Frascarelli Sabina,
Ronca Francesca,
RoncaTestoni Simonetta
Publication year - 2002
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.02-0402fje
Subject(s) - ryanodine receptor , thapsigargin , chemistry , endoplasmic reticulum , calmodulin , sarcolemma , protein kinase c , protein kinase a , chelerythrine , medicine , trpc3 , endocrinology , nifedipine , calcium , biophysics , kinase , myocyte , biochemistry , biology , trpc , receptor , transient receptor potential channel , organic chemistry
We investigated whether changes in cardiac work or in Ca 2+ fluxes may affect the expression of sarcolemmal or sarcoplasmic reticulum Ca 2+ channels (DHPRs and RyRs, respectively). Isolated rat hearts were perfused at low Ca 2+ concentration (0.8 mM instead of 1.5 mM), at low preload (5 cm instead of 20 cm), in the presence of 100 nM nifedipine or with a cardioplegic solution. After 60 min, hypocalcemic perfusion produced significant reduction in [ 3 H]‐PN 200–110 and [ 3 H]‐ryanodine binding, due to ≈30% reduction in Bmax (P<0.01), with unchanged Kd. Such modifications were reversible. Similar results were obtained in the nifedipine and cardioplegia groups. Low preload perfusion produced similar contractile effects as hypocalcemic perfusion, but it had no effect on radioligand binding. After hypocalcemic perfusion, DHPR and RyR gene expression, evaluated by RT‐PCR, were not modified. Chelerythrine (protein kinase C inhibitor) and lavendustin C (Ca 2+ /calmodulin‐dependent protein kinase II inhibitor), but not H‐89 (protein kinase A inhibitor), abolished the effects of hypocalcemic perfusion on [ 3 H]‐PN 200–110 and [ 3 H]‐ryanodine binding. We conclude that reduced Ca 2+ entry and/or intracellular Ca 2+ cycling determines DHPR and RyR remodeling through posttranslational protein modifications. Both protein kinase C and Ca 2+ /calmodulin‐dependent protein kinase II appear to play a role in this phenomenon.