Question

14. Duchenne’s Muscular Dystrophy (DMD) is a rare, genetic disorder of the skeletal muscle that results in muscle weakness (myotonia; reduced muscle tone) and muscle wasting. An X-linked recessive disorder, it is most commonly observed in males, and can be diagnosed typically when a baby takes its first steps. Paradoxically, infants with DMD exhibit increased muscle tone. The mechanism for this increase in muscular activity is thought to be the absence of dystrophin. For reasons that are not entirely clear, the absence of this protein permits Ca2+ to enter the sarcoplasm.

    1. (a) (10 points) What are the steps that normally lead to muscle contraction? In your answer, assume that the neurotransmitter has been released. Starting with the name of that transmitter, describe the relevant steps. Please be sure to include a discussion of what receptors in the process are doing (and how they do it) and how tension is generated, because that is part of the process.

    2. (b) (6 points) What is the role of Ca2+ in that process? How would the excess Ca2+ modify that process? In other words, what would having too much Ca2+ mean for muscle. You should assume that, in this pathological state, the muscle does not undergo fatigue.

    3. (c) (2 points) Once the disease progresses and muscles die, patients typically need to be put on a ventilator. Why would this be the case? For full credit, you must state what the diaphragm is used for, how that would be affected in DMD, and what the ventilator allows them to do.

Answer 1

a. The nerves bring nerve impulse to the neuromuscular junction. The motor end plate nea the neuromscular junction will releases Acetyl Choline neurotransmitter. Release of Acetyl Choline will stimulate the muscle membrane sarcolemma. The stimulation or the wave of depolarization is carried to the interior of the muslce thorugh T-tubules of the sarcolemma, Sarcoplasmic reticulum releases Ca ions. Release of Ca ions will start the beginning of the muscle conntraction. The Ca ions bind to Tropnin of the secondary filaments. The binding of Ca to troponin exposes the active sites of the secondary filaments by pulling tropomysin away from the active sites of the Actin monomers. Once the active sites are exposed, cross bridges present on the primary filaents hold on to active sites and pull them towards the H zone. Sarcoplasm size reduces with more and more drawing of the secondary filaments in to the H zone. When muscle has completely contracted, there is no H xone. This is how the sarcomere size reduces and this results in muscle contraction as sarcomere is the structural and functional unit of a muscle.

b. Ca is very important in muscle contraction. The process of muscle contraction starts with the release of Ca. The Ca ions bind to troponin present in the secondary filaments resulting in the exposure of the active sites of the actin monomers. This happens because tropomyosin filaments are pulled apart from their position in the secondary filaments.Exposure of the active sites on actin monomers will lead to binding of the cross bridges with acive sites and pulling the secondary filaments in to A band resulting muscle contraction.

Excess Ca ions will lead to continued muscle contraction and rigidity. In some cases it also can result in myofibril disorientation, mitochondrial damage and weakness. Prolonged physiological elivated levels will also cause slowing of relaxation.

c. Muscle contraction is important for various physiological functions of the body. Respiration , heart beating also need muscular contraction. Diaphram present beneath the muscles is very important respiratory muscle. Contraction of the diaphragm increases the thoracic cavity volume and results in inhalation. Relaxation of the diaphragm in the miscle results in decrease in the thoracic cavity volume bringing exhalation. So diaphragm is important for breathing. In a muscular defects when the muscles are not able to contract normally, physiological function of the body gets affected. In such a case a person is kept under ventilator.The ventilator will blow air in to lungs which helps in maintaining the O2 and Co2 levels in the blood in the absence of the breathing movements in the body.