Effect of cantharidin on contractility in mice overexpressing phospholamban in the atria

J. Neumann, L. Field, L. R. Jones

Research output: Contribution to journalArticle

Abstract

Phospholamban (PLB) inhibits the Ca2+ ATPase activity and hence inhibits Ca2+ uptake into the sarcoplasmic reticulum. PLB-phosphorylation by cAMP increasing compounds or phosphatase inhibitors increases Ca2+ uptake. Thus, we hypothesized that the relaxant properties of phosphatase inhibitors (like cantharidin, C) are dependent on the level of PLB expression. Transgenic mice (TG) that overexpress PLB in atria under control of the ANF promotor were produced. In isolated electrically driven left atria from control (Ctr) and TG, basal force of contraction amounted to 1.85 ± 0.44 mN and 0.47 ±0.12 mN, resp., which was increased by C concentration dependently, starting at 1 μM. The maximum effect by 100 μM C amounted to 4.1 ±5.4 mN (by 121 %) and 3.9 ±0.31 mN (by 730 %, n= 9 - 11), respectively. However, C inhibited phosphatase activity in a similar way in both TG and Ctr (IC50 about 10 nM). Under basal conditions total contraction time amounted to 83 ± 5 ms in TG and 62 ±7 ms in Ctr. In TG but not in Ctr 100 μM C decreased total contraction time by 19 %.

Original languageEnglish (US)
Pages (from-to)A414
JournalFASEB Journal
Volume10
Issue number3
StatePublished - Dec 1 1996

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ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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