muscles

Question 1

what is the incidence of myotonia?

Answer 1

1:23,000 to 1:50,000

Question 2

CLC0

Answer 2

Cl- channel in electrical eel

allows eel to generate electricity to stun prey

Question 3

where is the CLC1 Cl- channel specifically found in?

Answer 3

skeletal muscles

Question 4

what are the two types of myotonia congenita and what is the difference between them?

Answer 4

thomsen’s autosomal dominant myotonia congenita
beckers autosomal recessive myotonia congenita
whether 2 faulty alleles or 1 faulty allele is required to have the condition depends on the position of the mutation in the gene

Question 5

describe the structure of CLC1

Answer 5

12 TM spanning domains (4th domain may sit outside the cell)
4 CLC1 subunits = 1 functional channel

Question 6

what is the effect of the G200R mutation on CLC1 channel?

Answer 6

channel = functional
shift in voltage dependence - higher voltage needed than WT for a given open probability
resting membrane potential is less negative than WT because Cl- channels open less (loss of Cl- contribution to resting membrane potential) resting membrane potential is closer to threshold.
size of depolarisation needed to reach threshold smaller than required
patient fires APs more frequently and is more likely to fire APs when they should not

Question 7

how does CLC1 set the resting membrane potential?

Answer 7

1/2 of CLC1 Cl- channels are open
CLC1 open probability increases as membrane potential depolarises - pulls membrane potential back to a more negative value

Question 8

what mutation causes paramyotonia?

Answer 8

GOF mutation in SCN4A –> makes Nav1.4

found in skeletal muscles

Question 9

how does cold trigger paramyotonia?

Answer 9

cold slows down the kinetics of the Nav1.4 channel
this is enhanced in the mutated channel due to structural changes
greater time period during which Na+ enters the muscle fibre

Question 10

what is tachypnea?

Answer 10

increase in breathing rate

Question 11

what are the consequences of malignant hyperthermia after being exposed to general anaesthetics without treatment?

Answer 11

hyperkalaemia - muscle rigidity results in breakdown of muscle fibre. release intracellular K+ -> high plasma K+. impacts cardiac and neuronal excitability = tachycardia. death.
low plasma O2 because increased O2 used to make ATP required to sustain ATP levels
lactic acidosis - low plasma O2 so undergo anaerobic respiration. produces lactic acid = metabolic acidosis.
respiratory acidosis - problems with skeletal muscles involved in breathing + increased metabolism leading to high plasma CO2
tachycardia because of need to increase O2 supply

Question 12

how does malignant hyperthermia result in a rise in body temperature?

Answer 12

excessive muscle contraction (a lot of cross bridge formation) results in increased ATP hydrolysis which produces heat
more ATP is made to replenish ATP stores which also produces heat
= hypermetabolic state of muscles

Question 13

what is the most common mutation in the RyR1 channel in humans?

Answer 13

at position 614

Question 14

what mutation causes malignant hyperthermia?

Answer 14

GOF mutation in RyR1

increase in open probability –> bigger currents –> more Ca2+ leaving sarcoplasmic reticulum –> bigger contraction

Question 15

Porcine stress syndrome

Answer 15

malignant hyperthermia in pigs caused by arginine to cysteine mutation at position 615 in RyR1

Question 16

DEFINE: motor unit

Answer 16

motor neuron AND the muscle fibres it innervates

Question 17

describe an action potential at the neuromuscular junction

Answer 17

1. depolarisation mediated by voltage gated Na+ channels. spreads down axon to pre-synaptic terminal.
2. voltage gated Ca2+ channels on pre-synaptic membrane open
3. increase in intracellular Ca2+ drives fusion of vesicles containing ACh with pre-synaptic membrane
4. ACh released and binds to nicotinic ACh receptors at post-synaptic membrane
5. depolarisation of post-synaptic membrane activates voltage gated Na+ channels which mediates muscle action potential
6. L type voltage gated Ca2+ channels activated and Ca2+ released from sarcoplasmic reticulum
7. influx of Ca2+ into muscle fibre triggers muscle contraction
8. voltage gated K+ channels on muscle fibre membrane mediate repolarisation

Question 18

what is the length of a neuronal and muscle action potential?

Answer 18

1-2ms

Question 19

what is the Nernst potential of nicotinic AChR?

Answer 19

0mV

Question 20

Nicotinic AChR

Answer 20

non selective ligand gated cation channel
5 subunits make up 1 receptor
key subunits = 2α and β
2 ACh binding sites - 2 ACh must bind for the receptor to open
4 TM domains
N and C termini project extracellularly

Question 21

which gene codes for the α subunit of nicotinic AChR in muscle

Answer 21

CHRNA1

Question 22

which gene codes for the α subunit of nicotinic AChR in neuronal tissue

Answer 22

CHRNA2-8

Question 23

which gene codes for the β subunit of nicotinic AChR in muscle?

Answer 23

CHRNB1

Question 24

which gene codes for the β subunit of nicotinic AChR in neuronal tissue?

Answer 24

CHRNB2-4

Question 25

Myasthenia gravis

Answer 25

autoimmune disease
antibodies produced against α1 subunit and β1 subunit of nicotinic AChR so targets muscle - blocks from working
reduced number of AChR on post synaptic membrane
reduced AP firing –> reduced muscle contraction

Question 26

Transverse tubules

Answer 26

membrane invaginations found in skeletal and cardiac muscle

Question 27

what is a triad?

Answer 27

transverse tubule and sarcoplasmic reticulum on either side of the transverse tubule

Question 28

what is Ca2+ induced Ca2+ release?

Answer 28

Ca2+ coming in from outside of the cell activates ryanodine receptors on sarcoplasmic reticulum
Ca2+ is released from the store

Question 29

Ca2+ reuptake mechanisms

Answer 29

Ca2+ ATPase on plasma membrane - actively pumps Ca2+ out of the cell in exchange for H+
Na+/Ca2+ exchanger - Ca2+ moves out of the cell in exchange for Na+ inside the cell. driving force providing by Na+/K+ ATPase
Ca2+ ATPase on sarcoplasmic reticulum - actively pumps Ca2+ into sarcoplasmic reticulum in exchange for H+ out
Ca2+ binding proteins e.g. calreticulin and calsequestrin - found in sarcoplasmic reticulum and holds a lot of Ca2+

Question 30

what forms the Z line?

Answer 30

α-actinin