Phospholamban: A major determinant of the cardiac force-frequency relationship

Wolfgang F. Bluhm, Evangelia G. Kranias, Wolfgang H. Dillmann, Markus Meyer

Research output: Contribution to journalArticlepeer-review

63 Scopus citations

Abstract

The cardiac force-frequency relationship has been known for over a century, yet its mechanisms have eluded thorough understanding. We investigated the hypothesis that phospholamban, a potent regulator of the sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA), determines the cardiac force-frequency relationship. Isolated left ventricular papillary muscles from wild-type (WT) and phospholamban knockout (KO) mice were stimulated at 2 to 6 Hz. The force-frequency relationship was positive in WT but negative in KO muscles, i.e., it was inverted by ablation of phospholamban (P < 0.01, n = 6 mice). From 2 to 6 Hz, relaxation accelerated considerably (by 10 ms) in WT muscles but only minimally (by 2 ms) in KO muscles (WT vs. KO: P < 0.0001, n = 6). To show that the lack of frequency potentiation in KO muscles was not explained by the almost maximal basal contractility, twitch duration was prolonged in six KO muscles with the SERCA inhibitor cyclopiazonic acid to WT values. Relaxation still failed to accelerate with increased frequency. In conclusion, our results clearly identify phospholamban as a major determinant of the cardiac force-frequency relationship.

Original languageEnglish (US)
Pages (from-to)H249-H255
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume278
Issue number1 47-1
DOIs
StatePublished - Jan 2000
Externally publishedYes

Keywords

  • Knockout mice
  • Papillary muscles
  • Rapid cooling contractures
  • Twitch acceleration

Fingerprint Dive into the research topics of 'Phospholamban: A major determinant of the cardiac force-frequency relationship'. Together they form a unique fingerprint.

Cite this