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Assessment of Myofilament Ca2+ Sensitivity Underlying Cardiac Excitation-contraction Coupling
08:29

Assessment of Myofilament Ca2+ Sensitivity Underlying Cardiac Excitation-contraction Coupling

Published on: August 1, 2016

Functional effects of protein kinase C-mediated myofilament phosphorylation in human myocardium

Jolanda van der Velden1, Nadiya A Narolska, Regis R Lamberts

  • 1Laboratory for Physiology, Institute for Cardiovascular Research, VU University Medical Center, Amsterdam, The Netherlands. j.vandervelden@vumc.nl

Cardiovascular Research
|December 27, 2005
PubMed

Insights

Protein kinase C (PKC) has a minor effect on maximal force in human heart muscle. However, PKC decreases calcium sensitivity, potentially improving diastolic function in heart failure by altering myofilament phosphorylation.

Area of Science:

  • Cardiovascular Physiology
  • Molecular Cardiology
  • Cardiac Muscle Function

Background:

  • Heart failure is associated with reduced beta-adrenergic signaling (Protein Kinase A - PKA) and increased Protein Kinase C (PKC) activity.
  • PKC-mediated phosphorylation of myofilament proteins may impair contractile function in cardiomyopathy.
  • Understanding PKC's role in human myocardium is crucial for developing targeted therapies.

Purpose of the Study:

  • To investigate the effects of PKC on human myofilament function.
  • To determine how PKC influences myofilament phosphorylation under basal conditions.
  • To examine the interplay between PKC, PKA, and phosphatase activity on myofilament function.

Main Methods:

  • Isometric force measurements in permeabilized human cardiomyocytes from failing and non-failing hearts.
  • Analysis of myofilament protein phosphorylation using gel electrophoresis and Western immunoblotting.
  • Assessment of PKC, PKA, and phosphatase treatments on myofilament Ca(2+) sensitivity and maximal force.

Main Results:

  • PKC slightly reduced maximal force in basal conditions, with minimal impact after PKA or phosphatase treatment.
  • PKC significantly decreased Ca(2+) sensitivity more in failing than non-failing cardiomyocytes.
  • PKC phosphorylated PKA sites on Troponin I and increased Troponin T phosphorylation, but did not alter myosin light chain phosphorylation.

Conclusions:

  • PKC-mediated myofilament phosphorylation has a limited effect on maximal force in human myocardium.
  • The observed decrease in Ca(2+) sensitivity by PKC may enhance diastolic function in heart failure.
  • This effect is relevant in failing hearts where PKA-mediated Troponin I phosphorylation is diminished.
Abstract

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