Lecture 14: MUSCLE PHYSIOLOGY (part 2) Flashcards
Control of cross bridge cycling: Role of Ca2+
1.ACTIN,
- TROPONIN COMPLEX
- TROPOMYSOIN
- TROPOMYOSIN BLOCKING MYOSIN BINDING SITE
- BINDING SITE EXPOSED BY Ca_2 MEDIATED TROPOMYOSIN MOVEMENT
Control of skeletal muscle contraction
(Excitation-contraction coupling). = 6
- Troponin →
- tropomyosin moves
- → exposes myosin
- binding sites (actin)
- → crossbridge cycling
- → contraction
Modulation of E-C Coupling:
1. Effect of TNFα on Ca2+ signalling in muscle fibres
- TNFa is an inflammatory cytokine that is elevated after
muscle injury and though to contribute to post injury muscle weakness. - However, the mechanism
responsible was unknown. - In cardiac muscle, alterations to Ca2+ signalling were
reported to be a major factor in the loss
of contractile force induced by exposure to TNFa.
Hypothesis:
TNFa is altering force in skeletal muscle by altering SR Ca2+ release in skeletal muscle.
- Changes in intracellular Ca2+ can be measured in living cells using
chemical fluorescent Ca2+ indicators such as fura-2. - Fluorescent Ca2+ indicators change conformation upon binding Ca2+
and this results in a change in fluorescence emission intensity, which
can be measured and used as an estimate of the change in Ca2+ - Indicator is membrane permeable, and becomes trapped in the cell.
Modulation of skeletal muscle contraction:
Role of TNFα
- Changes in peak Ca2+ indicate Changes in SR Ca2+ release
- Changes in the slope of the Ca2+ decay indicate changes in SR Ca2+ uptake.
SR Ca2+ release (–) and reuptake (–) in response to a single action
potential in a living skeletal muscle fibre measured using a flura-2.
Effect of TNFα on Ca2+ signalling in muscle fibres METHODS…3
1 * Cultured muscle cells exposed to either a TNF or a control solution for 48 hours.
2 * Muscle cells loaded with Fura-2 and stimulated to contract via
platinum electrodes.
3 * Fura-2 fluorescence measured using a spectrophotometer.
The effect of the inflammatory cytokine TNFα on Ca2+ release in skeletal muscle cells
TNFa:
1 * Decreases both SR Ca2+ release and Ca2+ uptake → muscle weakness.
2 * TNFa may be protective – preventing overuse of injured muscle.
Taurine:
1 * A sulphonic amino acid
2 * Found only in animal kingdom
3 * Found in especially high concentrations in excitable cells
e.g. Skeletal muscle, heart, nerves (and some smooth muscle).
Known effects of taurine:
- osmoregulation
- modulation of ion channel activity (increases & decreases reported).
Effect of Taurine on ECC in skeletal muscle
Skeletal muscle has high taurine content ( approx 40 mM) but its role in
modulation of force production was unknown
Hypothesis:
Taurine increases force production in skeletal muscle
by increasing SR Ca2+ release.
methods…problem and solution
- Problem:
Taurine is not membrane permeable, and therefore,
taurine cannot easily removed or added to a fibre. - Solution:
Use the skinned fibre technique
* Unique preparation to study nearly all aspects of ECC.
* Muscle membrane (Sarcolemma) mechanically removed.
* Provides access to intracellular environment.
skinned fibres
just understand it
Effect of taurine on the size of the depolarisation-induced force responses
1 * 20 mM Taurine increases force by 20% in skeletal muscle.
2 * Conclusion: Taurine enhances for production in skeletal muscle
Taurine implications for ATHLETES…
- Meat products are high in taurine, and modest meat
consumption should supply adequate amounts of taurine.
- Meat products are high in taurine, and modest meat
- Vegetarian athletes may want to supplement
their diet with taurine (Synthetic taurine is available).
- Vegetarian athletes may want to supplement
- Humans can also manufacture some taurine.
Basic muscle contraction types: ISOTONIC VS ISOMETRIC
A. Isotonic contraction:
Muscle shortens, while
load remains constant.
Work can is accomplished.
B. Isometric contraction:
Muscle develops tension but does not shorten (constant length) . No work is done
