Impressive was a champion Quarter Horse stallion with a magnificent muscular physique, a trait that he passed on to dozens of offspring. However, many of Impressive's offspring developed periodic muscular twitching that sometimes left the horses temporarily unable to move. Some horses even died. As it turns out, Impressive's award-winning physique was due to a mutation in a single, protein-encoding gene, resulting in hyperexcitable muscle (which contracts even in the absence of a stimulus from its motor neuron). Which is NOT a plausible explanation for the identity of the abnormal muscle protein in Impressive and his offspring?

Question

A.  tropomyosin that is unable to bind to actin
B.  acetylcholine receptors that function in the absence of acetylcholine
C.  over-active troponin molecules
D.  leaky Na+ channels
E.  overactive Ca2+ pumps in the membrane of the sarcoplasmic reticulum

Clarify Question
· What is the key concept addressed by the question?
· What type of thinking is required?

Gather Content
· What do you know about excitation of muscles? What other information is related to the question?

Choose Answer
· Given what you now know, what information is most likely to produce the correct answer?

Reflect on Process
· Did your problem-solving process lead you to the correct answer? If not, where did the process break down or lead you astray? How can you revise your approach to produce a more desirable result?

Answer 1

E.  overactive Ca2+ pumps in the membrane of the sarcoplasmic reticulum

Clarify Question
· What is the key concept addressed by the question?
        o The question asks about excitation of muscles.
· What type of thinking is required?
        o You are being asked to analyze statements about what could cause hyperexcitable muscles.

Gather Content
· What do you know about excitation of muscles? What other information is related to the question?
        o When a nerve signal reaches a muscle the neurotransmitter, acetylcholine, is released at a neuromuscular junction and then binds to acetylcholine receptors that, in turn, open Na+ channels. This causes the muscle cell membrane to depolarize. This depolarization is conducted along the muscle cell membrane and down the transverse tubules to stimulate the release of Ca2+ from the sarcoplasmic reticulum. Ca2+ diffuses through the cytoplasm to myofibrils, causing contraction. When the muscle is at rest, a long filament of the protein tropomyosin blocks the myosin-binding sites on the actin molecule. Because myosin is unable to form cross-bridges with actin at these sites, muscle contraction cannot occur. When Ca2+ binds to another protein, troponin, the Ca2+–troponin complex displaces tropomyosin and exposes the myosin-binding sites on actin, permitting cross-bridges to form and contraction to occur.
        o When impulses from the motor neuron cease, it stops releasing acetylcholine, in turn stopping the production of impulses in the muscle fiber. Another membrane protein in the sarcoplasmic reticulum then uses energy from ATP hydrolysis to pump Ca2+ back into the sarcoplasmic reticulum by active transport. Troponin is no longer bound to Ca2+, so tropomyosin returns to its inhibitory position, allowing the muscle to relax.

Choose Answer
· Given what you now know, what information is most likely to produce the correct answer?
        o A hyperexcitable muscle  would be excited even in the absence of a stimulus. So if Na+ ions can cross the muscle cell membrane through a leaky Na+ channel, or if acetylcholine receptors can function in the absence of acetylcholine, this could allow the muscle to be excited in the absence of a signal. Also inactive tropomyosin or over active troponin could lead to hyperexcitability.This is because  tropomyosin binds to actin preventing myosin binding in the absence of Ca2+. Alternatively when Ca2+ is present troponin displaces tropomyosin allowing actin and myosin to bind and contraction to occur.
        o The correct answer is that overactive Ca2+ pumps in the membrane of the sarcoplasmic reticulum would not lead to hyperexcitability as these pumps would remove Ca2+ from the muscle cell cytoplasm and decrease excitability. So an overactive Ca2+ pump would decrease muscle contractions.

Reflect on Process
· Did your problem-solving process lead you to the correct answer? If not, where did the process break down or lead you astray? How can you revise your approach to produce a more desirable result?
        o This question asked you to analyze statements about what could cause hyperexcitable muscles. If you got the correct answer, great job! If you got an incorrect answer, where did the process break down? Did you think that blocking the troponin/tropomyosin reaction would lead to hyperexcitability? Did you think that decreased Na+ movement across the membrane would lead to hyperexcitability?