B: Muscle contraction

Question 1

Process of muscle contraction —

Answer 1

• Nervous system signal causes depolarization of t-tubule
• Causes conformational change in voltage sensitive protein in t-tubules called dihydropyridine receptor (DHPR)
• DHPR is linked to RYR1 Ca++ release channel in SR and change causes RYR1 Ca++ release channel to open.
• Large amounts of Ca++ flow out of SR through RYR1 channel into myoplasm and cause contraction
• Relaxation occurs when Ca++ is pumped back into SR and out of cell by Ca++ ATPase pump.
• This pumps Ca++ up gradient so needs 1 ATP per 2 Ca++ pumped.
• Some Ca++ is pumped out of cell by Na+/Ca++ exchanger in plasma membrane.

Question 2

Familial hypertrophic cardiomyopathy: —

Answer 2

Heart muscles enlarge, causing walls of ventricles to thicken + block blood flow. Can also cause blood to leak backwards through mitral valve.

Caused by change of amino acid in myosin protein due to a missense mutation (replacement of one amino acid with a different amino acid) in MYH7 gene.

Question 3

Malignant hyperthermia —

Answer 3

RYR1 Ca++ release channel is leaky - calcium leaks out of SR onto myofibril causing increased contracture - consumes ATP and generates heat.
When anaesthetics are given to patient, there is a rapid increase in body temperature + metabolism + contracture of skeletal muscle. Increase metabolism causes tachycardia + increase CO2 production which can lead to acidosis.

Question 4

Central Core Disease (CCD) —

Answer 4

RYR1 Ca++ release channel is leaky- lower concentration of Ca in SR and higher basal level of Ca in myoplasm.

Muscle weakness disorder.

Question 5

Hypokalemic period paralysis —

Answer 5

Mutation in one of the subunits of DHPR –> defective in sensing depolarisation so cannot activate ryanodine receptor efficiently. This leads to attacks of muscle weakness/ paralysis

Question 6

Brody’s disease —

Answer 6

Mutation in Ca++ ATPase –> causes muscle cramping and stiffening after exercise + strenuous activity.

Question 7

Mutations in RYR2 gene

Answer 7

Can cause CPVT - change in function and structure of RYR2 gene can disrupt careful flow of calcium ions in myocytes –> triggers an abnormal heart rhythm.
Other mutations in RYR2 can cause ARVC –> heart muscle breaks down over time.

Question 8

RYR1 vs RYR2

Answer 8

RYR1 - main one for skeletal muscle
RYR2 - main for cardiac + smooth

Question 9

How is calcium pumped back into SR

Answer 9

• Via Ca2+ ATPase pump (SERCA)
• Uses 1 ATP per 2 Ca2+ pumped.
• Some is pumped out by Na+/Ca2+ exchanger in plasma membrane.

Question 10

What is excitation-contraction coupling?

Answer 10

Coupling between neuronal excitation and contraction through DHPR and RYR1 Ca2+ channel, resulting in Ca2+ release and muscle contraction.

Question 11

Note on familiar hypertrophic cardiomyopathy

Answer 11

• Most common inherited heart disease + cause of sudden cardiac arrest in young people/ athletes
• 1 in 500
• Autosomal dominant
• Heart muscles enlarge, causing walls of ventricles to thicken + block blood flow. Can also cause blood to leak backwards through mitral valve.
• Symptoms include: dizziness, shortness of breath, fainting, serious arrhythmias
• ## Caused by change of amino acid in myosin protein due to a missense mutation (replacement of one amino acid with a different amino acid) in MYH7 gene.