Excitation Contraction Coupling (ECC)

Question 1

what is myasthenia gravis caused by?

Answer 1

autoimmune response to ACh receptors (neuromuscular junction disease) so cannot initiate AP in muscle
-ptosis, weak smile, diploplia, speech slur symptoms: improve with edrophonium chloride (cholinesterase inhibitor to increase ACh at neuromuscular junction)

Question 2

what is ALS amyotrophic lateral sclerosis a disease of?

Answer 2

motor neuron death in spinal cord

• loss of neuronal AP (reduced excitation)
• weakness, spasticity, muscle atrophy

Question 3

what are demyelinating diseases caused by?

Answer 3

peripheral nerve disease b/c autoimmune VS myelin

• impaired neuronal AP propagation (reduced excitation)
• ascending paralysis, weakness

Question 4

what is muscular dystrophy a disease of?

Answer 4

muscle disease (reduced attachment of muscle to ensheathing membrane)

• inefficient myofiber contraction, myofiber death (reduced contraction)
• muscle weakness and atrophy

Question 5

what is malignant hyperthermia a disease of?

Answer 5

sarcomere disease (mutation of ryanodine receptor Ryr1 causing excessive Ca++ release into muscle)

• triggered by inhaled anesthetics
• excessive and prolonged myofiber contraction
• blood CO2 buildup, hyperthermia, circulatory collapse

Question 6

can skeletal muscle contract in the absence of extraccellular Ca++?

Answer 6

yes, b/c Na+ dependent AP triggered by ACh release at neuromuscular junction triggers release of Ca++ from SR inside muscle cell/fiber

Question 7

dihydropyridine (DHP) receptor

Answer 7

L-type Ca++ channel on T-tubule membrane, attached to ryanidine receptors of terminal cisternae
-changes structure with depolarization, to open ryanodine receptor channel gate

Question 8

ryanodine receptor

Answer 8

Ca++ release channel attached to terminal cisternae

• opened by DHP receptor during depolarization
• causes Ca++ release into sarcoplasm, triggering sarcomere contraction

Question 9

ryanodine and nanomolar and micromolar concentrations

Answer 9

[nanomolar] - binds to and opens ryanodine receptors

[micromolar] - closes ryanodine receptors

Question 10

calcium induced calcium release (positive feedback)

Answer 10

SR releases Ca++ store rapidly

• ryanodine receptors open via DHP receptors and presence of cytoplasmmic Ca++
• this means that small amount of Ca++ released into sarcoplasm triggers adjacent ryanodine receptors (away from triad) to open and release Ca++ in positive feedback motion
• thus, Ca++ release occurs rapidly along entire length of SR, not just triad

Question 11

what induces skeletal muscle relaxation?

Answer 11

when Ca++ is removed from sarcoplasm by Ca++ exchangers and pumps

Question 12

mechanisms of Ca++ removal from sarcoplasm (3 types)

Answer 12

SERCA - uses ATP hydrolysis to pump Ca++ back into SR to be bound
PMCA - plasma membrane Ca++ ATPase that pumps 1 Ca++ out of the cell per 1 ATP
NCX - Na+ Ca++ exchanger that lets 3 Na+ into cell per 1 Ca++ out of cell

Question 13

unfused tetanus

Answer 13

repetitive stimulation (summation) APs oscillate (hit AP during refractory period, but not soon enough to fuse)

Question 14

what is the strength of contraction of skeletal muscle graded by? (3 things)

Answer 14

1. rate ccoding, or frequency of stimulation
2. recruitment of additional motor units
3. size of motor units stimulated

Question 15

fused tetanus

Answer 15

repetitive stimulation (summation) APs don’t oscillate (hit AP during refractory period soon enough to fuse)

Question 16

treppe

Answer 16

steady increase in tension in successive twitches

• not summation, b/c tension returns to zero before next twitch
• occurs b/c Ca++ released from previous twitches excceeds Ca++ reuptake, causing increase in Ca++ concentration, thus increasing X-bridges that form
• also b/c frequent stimulation “warms up” muscle to increase enzymatic rate

Question 17

what does Ca++ bind to within SR?

Answer 17

calreticulin and calsequestrin

Question 18

what is a motor unit made of?

Answer 18

one motor neuron and multiple myofibers
-a single neuron will innervate multiple muscle fibers, but a single skeletal muscle fiber is innervated by only one neuron

Question 19

small VS large motor units

Answer 19

small: single neuron and as few as 3 muscle fibers (extraoccular), in slow twitch
large: single neuron and 2000+ muscle fibers, in fast twitch
when motor unit activated, all innervated muscle fibers simultaneously stimulated

Question 20

what is the order of small/large motor unit recruitment

Answer 20

Size principle - smaller motor units recruited first, then larger ones as more force is required
-fine control possible if recruit only few muscle fibers

Question 21

how long does the energy supplied by ATP last?

Answer 21

1-2 seconds

Question 22

how does phosphocreatine make ATP, and how long does its energy last?

Answer 22

PCr + ADP –> Cr + ATP

lasts 5-8 seconds

Question 23

how does fermentation of glucose make ATP, and how long does its energy last?

Answer 23

glucose –> 2 lactic acid + 2 ATP

lasts 60 seconds (limited by lactic acid formation, not glucose amount)

Question 24

how does oxidative metabolism of glucose make ATP, and how long does its energy last?

Answer 24

glucose + 6 O2 –> 6 CO2 + 6 H2O + 30 ATP

lasts 2-4 hours

Question 25

how does oxidative metabolism of fats/CHO/PRO make ATP, and how long does its energy last?

Answer 25

FA + O2 --> CO2 + H2O + ATP AA + O2 --> CO2 + H2O + urea + ATP lasts many hours

Question 26

muscle pain (burn)

Answer 26

due to lactic acid buildup when heavy muscle activity and low O2 cause muscle to reoly on fermentation to make ATP - lactic acid accumulates in muscle fiber (burning) - in heart = angina

Question 27

what is angina?

Answer 27

buildup of lactic acid in cardiac muscle, b/c it is undergoing fermentation due to heavy activity and low O2

Question 28

delayed onset muscle soreness

Answer 28

not correlated with lactic acid levels - occurs in days following intense muscle use - associated with muscle damage, maybe inflammatory response

Question 29

muscle fatigue

Answer 29

decline in muscle tension due to muscle use, gradual depletion of SR Ca++ stores, and buildup of lactic acid and inorganic phosphates - less maximal tension - decreased shortening velocity (Vmax) - slower rate of relaxation - not due to low ATP - may be adaptation to prevent rigor from low ATP level

Question 30

what does low ATP favor?

Answer 30

stable actin myosin complexes, high Ca++ levels in sarcoplasm, thus rigor

Question 31

high frequency fatigue

Answer 31

accompanies high intensity, short duration exercise - due to failure in conduction of AP in T-tubule - rapid recovery

Question 32

low frequency fatigue

Answer 32

caused by low intensity, long duration exercises - due to buildup of lactic acid and phosphates, which may change conformation of muscle PRO - recovery is slow