Muscle Contraction and Dysfunction

Question 1

Contraction

Answer 1

the interaction of actin & myosin

• fuelled by ATP
• driven by a rise in [Ca2+]

Question 2

contractile cycle

Answer 2

diagram

Question 3

What causes the rise in calcium?

Answer 3

diagrams

Question 4

Sometimes it goes wrong

Answer 4

Multiple sclerosis
Myaesthesia gravis
Non-dystrophic myotonias
Muscular dystrophy

Question 5

Multiple sclerosis

Answer 5

diagrams
Immune attack of myelin
Leaky blood brain barrier
Sclerotic lesions
-Numbness
-Tingling
-Speech problems
-Visual problems
-Debilitating muscle weakness

Question 6

Myaesthesia Gravis

Answer 6

Progressive loss of nicotinic acetylcholine receptor
Auto-immune
Targeting the 1 subunit
diagrams

Question 7

Non-dystrophic myotonias

Answer 7

Features:
Delayed relaxation of the muscle after voluntary
contraction or mechanical stimulation.

Electrophysiologically characterized by highly
organized repetitive electrical activity of the
muscle fibres

Five different skeletal muscle disorders are caused by mutations to
the SCN4A gene:
Potassium-aggravated myotonia (PAM),
Paramyotonia congenita (PMC)
Hyperkalemic periodic paralysis (HyperPP),
Hypokalemic periodic paralysis (HypoPP),
A form of congenital myasthenic syndrome (CMS)

In most cases, mutations cause:
decreased rate of channel inactivation
increased rate of recovery from inactivation

OR
slower channel deactivation

More Na channel activity =
Prolonged contraction

Some examples are due to loss of Cl channel (CLC-1)

Less Cl channel activity =
Prolonged contraction

Question 8

Dystrophic myopathy

Answer 8

-The dystrophin gene is the largest gene yet identified in humans containing 79
exons and spanning > 2,200 kb = ~0.1% of genome
-Located in the short arm of the X chromosome
-Duchenne = total loss of dystrophin
-Becker =reduced or dysfunctional
dystrophin
-increased permeability to macromolecules
abnormal permeability is made worse by mechanical
stress.
-Muscle fibre necrosis, fibrosis and fat inflitration