Ablation of phospholamban in isolated mouse papillary muscles inverted the cardiac force-frequency relationship from positive to negative (P<0.01) and blunted relaxation acceleration (P<0.0001).
Ablation of phospholamban inverts the cardiac force-frequency relationship, identifying it as a major determinant of this physiological mechanism.
Absolute Event Rate: 2% vs 10%
p-value: p=<0.0001
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 Ca(2+)-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.
Bluhm et al. (Sat,) conducted a other in Cardiac force-frequency relationship. Phospholamban knockout vs. Wild-type was evaluated on Acceleration of relaxation from 2 to 6 Hz (ms) (p=<0.0001). Ablation of phospholamban in isolated mouse papillary muscles inverted the cardiac force-frequency relationship from positive to negative (P<0.01) and blunted relaxation acceleration (P<0.0001).