Excitation-Contraction Coupling

Question 1

Excitation-Contraction Coupling

Answer 1

Events that occur between the electrical depolarization of the sarcolemmal
membrane of a myocyte and the subsequent development of force and
shortening in a myocyte

Question 2

Excitation-Contraction Coupling Hypothesises

Answer 2

• The ‘Diffusion’ Hypothesis
• The Specialised Conducting Pathway Hypothesis
• Mechanical Coupling Hypothesis
• Calcium-Induced Calcium Release
• Chemical Messenger Hypothesis

Question 3

The ‘Diffusion’ Hypothesis {Proven wrong}

Answer 3

“Post-synaptic excitation releases some substance from the sarcolemmal
membrane that diffuses into the centre of the cell causing contraction”

Question 4

Experimental results of The ‘Diffusion’ Hypothesis

Answer 4

only calcium caused contraction out of ions . but insufficient time for diffusion of calcium to centre of cell. also injection of ca into cell only produced localised contraction.
== Ca is activativing substance but not through diffusion

Question 5

The Specialized Conducting Pathway Hypothesis

Answer 5

Since neither diffusion nor current flow were implicated, it was hypothesized
that a specialized pathway existed to conduct the excitatory signal from the SL
to the myofilaments

Question 6

Experimental results of The Specialized Conducting Pathway Hypothesis

Answer 6

then:

o Should observe a highly localized contraction and no spread of depolarization
Tests showed contraction of a single sartorius muscle
fibre was localized to a single sarcomere only if
depolarization was effected at the centre of the I band. Implies Z-line could be the pathway
==Discovery of T-tubules/triads

Question 7

• Proteins Involved in EC Coupling

Answer 7

RyR1:
Calcium release channel of the SR membrane
Dihydropyridine Receptor (DHPR)

Question 8

Dihydropyridine Receptor (DHPR)

Answer 8

Voltage sensor
§ L-type calcium channels
§ In skeletal muscle have very slow activation kinetics
§ Are in close apposition with the SR calcium release channels (RYR1 in
skeletal muscle, RYR2 in cardiac)
§ Involved in protein-protein interaction with the large cytoplasmic
domain fo RYR1 (foor) on depolarization to bring about SR calcium
release in skeletal muscle
§ Bind and is modulated by calmodulin (CaM)

Question 9

RyR1:

Answer 9

RyRs exist as at the junctional
terminal cisternae of SR
• Cytosolic Mg inhibits skeletal RyR1 activation by calcium
• ATP stimulates RyR1 opening
• Voltage sensor activation overcomes the Mg inhibition

Question 10

Mechanical Coupling Hypothesis

Answer 10

Favoured hypothesis to explain EC coupling in skeletal muscle
§ Depolarisation of DHPR in the TT leads to a configurational change of
the RyR in the SR increasing its open state probability.
There is a high density of DHPR in the TT membrane opposite
the RyR in terminal cisternae.

Question 11

Calcium-Induced Calcium Release (CICR)

Answer 11

§ Favoured method in cardiac muscle
Calcium trigger influx during a depolarization-induced opening of a
voltage-sensitive calcium channel (DHPR, so called because it binds,
and is inhibited by dihydropyridines) in the TT membrane induces the
release of calcium from the terminal cisternae of the SR

Question 12

Chemical Messenger Hypothesis

Answer 12

Favoured method in smooth muscle
A voltage sensitive phospholipase-C in the TT membrane
activates the conversion of
(PIP2) to (IP3) which binds to its receptor
(IP3R) thereby activating a calcium channel in the SR membrane

Question 13

Features of Mechanical Coupling Hypothesis

Answer 13

(i) Rapid kinetics
o (ii) No dependence on current flow per s (i.e. a steep F-Em
relation)
o (iii) No reliance on diffusion of any substance from
sarcolemma
o (iv) Because of (i) and (ii), activation can occur in the
absence of calcium even in the presence of calcium
chelators

Question 14

Features of Calcium-Induced Calcium Release (CICR)

Answer 14

(i) Following depolarization, an influx of extracellular calcium
into the cell induces the release of calcium from the SR
• (ii) Depolarisation alone is insufficient
• (iii) Contractile activation can occur only in the presence of
extracellular calcium

Question 15

Experimental results of Chemical Messenger Hypothesis

Answer 15

Microinjection of IP3 into a single
skeletal muscle cell causes release of
calcium from intracellular stores,
Q10 of latency is close to actual
BUT
The IP3 cascade is commonly initiated hormonally
rather than nervously