This document discusses excitation-contraction coupling (EC coupling) in skeletal muscle. It begins by defining EC coupling as the process by which an action potential triggers muscle contraction through calcium ion release. It then describes how the action potential spreads through the T-tubule system and activates the dihydropyridine and ryanodine receptors, causing calcium release from the sarcoplasmic reticulum. This triggers the contraction sequence and binding of calcium to troponin. Relaxation occurs via reuptake of calcium into the sarcoplasmic reticulum by SERCA pumps. Differences in smooth and cardiac muscle EC coupling are also summarized.

1. Excitation Contraction Coupling
(EC Coupling)
- Akshay Gill
(Roll no. 17)
MBBS 2018

2. Objectives:
• What is EC coupling?
• The passage of the impulse
• The T tubule
• Mechanism of Calcium Release
• The contraction sequence
• Relaxation
• Differences in smooth muscles
• Differences in cardiac muscles
• Applied aspect

3. What is EC coupling?
• An action potential triggers the contraction of a
muscle cell.
• Calcium ions can regulate whether or not
contraction can occur.
• Thus, “the link reaction which is needed to link
muscle excitation (the depolarisation of the
action potential) to Ca++ release from the
sarcoplasmic reticulum is called excitation-
contraction coupling”.

5. The Passage of the Impulse
• After the conduction of the impulse through the
axons to the post-synaptic membrane via the
neuromuscular junction, there are
conformational changes leading to flux of Na+
ions inside the muscle fibre.
• Accumulation of Na+ within the cell commence
the depolarisation of the membrane, giving rise
to the end plate potential that keeps rising
towards an action potential threshold.

6. The action potential
that is crossing
neuromuscular
junction

8. The action potential spreads throughout the fibre
and specially within the T tubules. Deep inside
the muscle fibre

9. The T-tubule :
• The T tubules are tube-shaped
invaginations of the sarcolemma that
penetrate throughout the muscle fibre.
• The lumen of the T tubule is continuous
with the ECF, and the membrane
depolarisation during action potential
occurs across the T-tubule membrane.
• On either side of the T-tubule are swellings
of the sarcoplasmic reticulum (SR) called
the lateral sacs or terminal cisterns.

10. T tubule structure :-

11. How does depolarisation in the T-tubule
membrane open a Ca++ channel in the SR
membrane?
• Located in the T-tubule membrane, closely
associated with the foot of the SR Ca++ Channel,
is the T-tubule voltage sensor, better known
as, DHPR (dihydropyridine receptor).
• The impulse passes to the L tubules containing
another receptor – the RyR or Ryanodine
receptor.

12. • The voltage sensor, changes conformation in
response to the depolarisation of the action
potential, and causes opening of the - RyR
(Ryanodine receptor).
• This conformational change is transmitted to the
foot of the SR Ca++ Channel causing it to open,
and allowing Ca++ release.
• Thus, Ca++ ions are released and utilised during
contraction of the muscle fibres.

14. The Contraction Sequence that follows:
• The Ca++ that accumulates, is the reason for
initiation and maintenance of the contraction of
sarcomere.
• The free Ca++ binds with the troponin C protein
component of the thin actin filaments
introducing the active calcium-troponin
complex.

15. Binding of Ca++ to the troponin C

16. There is conformational change in troponin C, which
induces alternation in the conformation of the
tropomyosin protein.
Exposure of the myosin binding sites of the actin
filament.

17. Myosin head binds to the sites on the actin filament.
The release of ADP+iP are tightly coupled to the power
stroke, thus resulting in shortening of sarcomere.

19. Relaxation
• SERCA pump (Sarco- Endoplasmic Reticulum
Calcium ATPase pump) is the enzyme
responsible for relaxation.
• This enzyme pumps calcium back into the
sarcoplasmic reticulum from the cytosol.

20. Summary:

22. Differences in Smooth Muscles:
I. Calcium channel differences:
• Different channels releasing calcium from ECF
(RyR still exists though), depends on the type
of smooth muscles.
• Channels could be voltage-gated, ligand-gated,
second messenger-gated or mechanically-
gated.

23. II. Calcium entrance options:
• From gated channels, extracellularly
• From IP3
IP3 (inositol triphosphate) is a second
messenger that opens RyR channel which
releases calcium from SR.
III. Calcium binds to calmodulin.
IV. Activation of MLCK (Myosin-light-chain-
kinase), causes phosphorylation of the myosin
head.

24. Differences in Cardiac Muscles:
• Cells are coupled as electrical syncytium due to
high expression of gap junctions between the
cells.
• Gap junctions consist of 2 connexons, each made
of 6 connexins.
• T tubules are very well developed with moe
diameter
• DIAD is present, i.e. With 1-tubule, there is only
1 cistern.

25. Applied:
• Malignant hyperthermia:
It is due to the mutation in the RyR
located in the L-tubules.
Characterised by –
- increased body temperature
- increased muscular contractions and
muscle rigidity
- increased heart rate
- high fever