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June 8, 2010The Journal of Physiology49 citationsOpen Access

Length dependence of force generation exhibit similarities between rat cardiac myocytes and skeletal muscle fibres

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LHLaurin M. HanftKMKerry S. McDonald

Key Result

Protein kinase A (PKA)-mediated myofibrillar phosphorylation converted shallow length-tension relationships in rat cardiac myocytes to steeper, fast-twitch-like relationships.

Structured PICO

P
Population
Rat skinned left ventricular cardiac myocytes and fast-twitch and slow-twitch skeletal muscle fibres
I
Intervention
Calcium activation to yield 50% maximal force, and protein kinase A (PKA)-induced myofilament phosphorylation
C
Comparator
Comparisons between cardiac myocytes, fast-twitch skeletal muscle fibres, and slow-twitch skeletal muscle fibres
O
Outcome
Sarcomere length-tension relationships and the sarcomere length dependence of force development (isometric force and rate constants (k(tr)) of force development)surrogate

Cardiac myocyte length-tension relationships can switch between slow-twitch-like and fast-twitch-like via PKA-mediated myofibrillar phosphorylation, suggesting a novel mechanism for controlling Frank-Starling relationships.

Abstract

According to the Frank-Starling relationship, increased ventricular volume increases cardiac output, which helps match cardiac output to peripheral circulatory demand. The cellular basis for this relationship is in large part the myofilament length-tension relationship. Length-tension relationships in maximally calcium activated preparations are relatively shallow and similar between cardiac myocytes and skeletal muscle fibres. During twitch activations length-tension relationships become steeper in both cardiac and skeletal muscle; however, it remains unclear whether length dependence of tension differs between striated muscle cell types during submaximal activations. The purpose of this study was to compare sarcomere length-tension relationships and the sarcomere length dependence of force development between rat skinned left ventricular cardiac myocytes and fast-twitch and slow-twitch skeletal muscle fibres. Muscle cell preparations were calcium activated to yield 50% maximal force, after which isometric force and rate constants (k(tr)) of force development were measured over a range of sarcomere lengths. Myofilament length-tension relationships were considerably steeper in fast-twitch fibres compared to slow-twitch fibres. Interestingly, cardiac myocyte preparations exhibited two populations of length-tension relationships, one steeper than fast-twitch fibres and the other similar to slow-twitch fibres. Moreover, myocytes with shallow length-tension relationships were converted to steeper length-tension relationships by protein kinase A (PKA)-induced myofilament phosphorylation. Sarcomere length-k(tr) relationships were distinct between all three cell types and exhibited patterns markedly different from Ca(2+) activation-dependent k(tr) relationships. Overall, these findings indicate cardiac myocytes exhibit varied length-tension relationships and sarcomere length appears a dominant modulator of force development rates. Importantly, cardiac myocyte length-tension relationships appear able to switch between slow-twitch-like and fast-twitch-like by PKA-mediated myofibrillar phosphorylation, which implicates a novel means for controlling Frank-Starling relationships.

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Cite This Study

Hanft et al. (2010) studied Frank-Starling relationship (rat model). Protein kinase A (PKA)-induced myofilament phosphorylation vs. Unphosphorylated state / skeletal muscle fibres was evaluated on Sarcomere length-tension relationships and rate constants (k(tr)) of force development. Protein kinase A (PKA)-mediated myofibrillar phosphorylation converted shallow length-tension relationships in rat cardiac myocytes to steeper, fast-twitch-like relationships.

synapsesocial.com/papers/6a0f5a827b46c501a19bcb51https://doi.org/10.1113/jphysiol.2010.190504
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Sarcomere length dependence of rat skinned cardiac myocyte mechanical properties: dependence on myosin heavy chain2007 · 58 citations
  2. 2Ca-dependence of isometric force kinetics in single skinned ventricular cardiomyocytes from rats1996 · 38 citations
  3. 3Factors influencing the ascending limb of the sarcomere length‐tension relationship in rabbit skinned muscle fibres.1987 · 73 citations
  4. 4Substitution of cardiac troponin C into rabbit muscle does not alter the length dependence of Ca2+ sensitivity of tension.1991 · 60 citations
  5. 5Differential effects of length on maximum force production and myofibrillar ATPase activity in rat skinned cardiac muscle.1994 · 48 citations