9 Muscles and Muscle Tissue: Part B

How IS contraction of a muscle cell turned on? I wanna hit a home run…..

A nerve cell (brain or spinal cord must signal a muscle cell! Myelinated axon of motor neuron Action potential (AP) Axon terminal of neuromuscular junction Nucleus Sarcolemma of the muscle fiber Action potential arrives at axon terminal of motor neuron. 1 Ca2+ Synaptic vesicle containing ACh Ca2+ Voltage-gated Ca2+ channels open and Ca2+ enters the axon terminal. 2 Mitochondrion Synaptic cleft Axon terminal of motor neuron Ca2+ entry causes some synaptic vesicles to release their contents (acetylcholine) by exocytosis. 3 Fusing synaptic vesicles Junctional folds of sarcolemma ACh Acetylcholine, a neurotransmitter, diffuses across the synaptic cleft and binds to receptors in the sarcolemma. 4 Sarcoplasm of muscle fiber ACh binding opens ion channels that allow simultaneous passage of Na+ into the muscle fiber and K+ out of the muscle fiber. 5 Na+ K+ Postsynaptic membrane ion channel opens; ions pass causing a brief depolarization and repolarization. ACh effects are terminated by its enzymatic breakdown in the synaptic cleft by acetylcholinesterase. 6 Ach– Degraded ACh Postsynaptic membrane ion channel closed; ions cannot pass so no further depolarization occurs. Na+ Acetyl- cholinesterase K+ Figure 9.8

WHY do the ions move the way they do? Why does Ca+ move INTO the nerve cell? Why does Na+ move INTO the muscle cell? Why does K+ move OUT of the muscle cell? HINT: you learned this in General Biology OUTSIDE IN IN Lo Na+ Lo Cl- Lo Ca+ Hi K+ Hi Na+ Hi Cl- Hi Ca+ Lo K+ Lo Na+ Lo Cl- Lo Ca+ Hi K+

Ions flow from HI to LOW down their concentration gradient. Ca++ is higher outside the cell, so tends to move into the cell. Na+ is higher outside the cell, so tends to move into the cell. K+ is higher inside the cell, so tends to move out of the cell. Very few ions move, so the concentrations don’t change. OUTSIDE IN IN Lo Na+ Lo Cl- Lo Ca+ Hi K+ Hi Na+ Hi Cl- Hi Ca+ Lo K+ Lo Na+ Lo Cl- Lo Ca+ Hi K+

RULES for ION MOVMENT Lo Na+ OCEAN Lo Cl- Hi Na+ Lo Ca+ Hi Cl- Hi K+ IONS FLOW FROM areas of High Concentration to Low Concentration In other words: IONS MOVE DOWN THEIR CONCENTRATION GRADIENT) In other words: IONS FLOW FROM HIGH TO LOW REMEMBER: The ocean (EC fluid) is salty (Lots of NaCl & CaCl2). The fish (cell) is just the opposite of the ocean (EC fluid). Salt tends to flow into the fish (cell). K+ tends to flow out of the fish (cell). Lo Na+ Lo Cl- Lo Ca+ Hi K+ OCEAN Hi Na+ Hi Cl- Hi Ca+ Lo K+ FISH

ACh opens chemical-gated channels, so small amount of Na+ enter the muscle. The cell to becomes very briefly POSTIVE (depolarization) To make an ACTION POTENTIAL requires voltage-gated channels to open, allowing much MORE Na+ in. Open Na+ Channel Closed K+ Channel Synaptic cleft Na+ ACh Na+ K+ K+ ACh + + + + + + + + + Action potential + Na+ K+ i o n + + t z a Generation and propagation of the action potential (AP) 2 a r i l p o d e o f e W a v Closed Na+ Channel Open K+ Channel Local depolarization: generation of the end plate potential on the sarcolemma 1 Na+ K+ 3 Sarcoplasm of muscle fiber Repolarization Figure 9.9

Why is it important to know how the NMJ works? It turns out that many toxins and poisons act on the neuromuscular junction. These toxins can produce two effects, both resulting in loss of muscle control: Flaccid paralysis – the muscle cannot contract at all. Tetanic paralysis – the muscle is in a constant, fully contracted state. Discuss the following questions with your neighbors, and then choose the appropriate answer.

Terminal cisterna of SR The action potential continues down the muscle cell, falling into a T tubule. Action potential is generated ACh Sarcolemma Terminal cisterna of SR Ca2+ Figure 9.11, step 1

At rest, the voltage inside the muscle cell is NEGATIVE, -------------. Axon terminal Open Na+ Channel Closed K+ Channel Synaptic cleft Na+ ACh K+ Na+ K+ ACh + + + + + + + + + n + Action potential o + + Na+ K+ a t i z r i l a o ------------ p d e o f v e W a 1 1 The cell is negative inside at rest Sarcoplasm of muscle fiber Figure 9.9, step 1

+ ACh is released and crosses the synapse. ACh binds to the ACh receptor. The receptor channel opens and allows Na+ to enter the cell Na+ is a positive ion and so the cell briefly becomes POSITIVE inside ++++++. Axon terminal Open Na+ Channel Closed K+ Channel Synaptic cleft Na+ + ACh + K+ Na+ K+ ACh + + + + + + n + Action potential + + + o + + Na+ K+ t i z a r i 2 a Generation and propagation of the action potential (AP) o l +++++ p d e o f e W a v 1 Sarcoplasm of muscle fiber Figure 9.9, step 2

The positive charge causes DIFFERENT Na+ channels to open, and more Na+enters, SO, the +++ charge is carried down the cell membrane Axon terminal Open Na+ Channel Closed K+ Channel Synaptic cleft Na+ + ACh + K+ Na+ K+ ACh + + + + + + + Action potential + + + n o + + Na+ K+ t i a r i z 2 a Generation and propagation of the action potential (AP) o l p d e o f v e W a 1 1 Local depolarization: generation of the end plate potential on the sarcolemma Sarcoplasm of muscle fiber Figure 9.9, step 2

+ THE TRAVELING POSITIVE CHARGE IS CALLED AN ACTION POTENTIAL. THE AP IS A SIGNAL THAT TURNS ON CONTRACTION (LIKE A DOORBELL) Axon terminal Open Na+ Channel Closed K+ Channel Synaptic cleft Na+ + ACh + K+ Na+ K+ ACh + + + + + + + Action potential + + + n o + + Na+ K+ t i a r i z 2 a Generation and propagation of the action potential (AP) o l p d e o f v e W a 1 1 Local depolarization: generation of the end plate potential on the sarcolemma Sarcoplasm of muscle fiber Figure 9.9, step 2

Ca++ is released from the SR into the cytoplasm The Action potential is a signal that moves along the sarcolemma and down the T tubules, and then Ca++ is released from the SR into the cytoplasm Steps in E-C Coupling: Sarcolemma Voltage-sensitive tubule protein T tubule Ca2+ release channel Terminal cisterna of SR Ca2+ Figure 9.11, step 3

Can you explain why calcium is able to diffuse OUT of the sarcoplasmic reticulum and into the cytoplasm of the cell? ? . T tubule Ca2+ release channel . Ca2+ Figure 9.11, step 4

Into the cytoplasm starts the thin and thick filament interaction. Steps in E-C Coupling: Sarcolemma Voltage-sensitive tubule protein T tubule 1 Action potential is propagated along the sarcolemma and down the T tubules. Calcium flowing Into the cytoplasm starts the thin and thick filament interaction. Ca2+ release channel Calcium ions are released. 2 Terminal cisterna of SR Ca2+ Actin Troponin Tropomyosin blocking active sites Ca2+ Myosin 3 Calcium binds to troponin and removes the blocking action of tropomyosin. Active sites exposed and ready for myosin binding 4 Contraction begins Myosin cross bridge The aftermath Figure 9.11, step 2

Actin Troponin Tropomyosin blocking active sites Ca2+ Myosin The aftermath Figure 9.11, step 5

3 Actin Troponin Tropomyosin blocking active sites Ca2+ Myosin Calcium binds to troponin and removes the blocking action of tropomyosin. 3 Active sites exposed and ready for myosin binding The aftermath Figure 9.11, step 6

3 4 Actin Troponin Tropomyosin blocking active sites Ca2+ Myosin Calcium binds to troponin and removes the blocking action of tropomyosin. 3 Active sites exposed and ready for myosin binding Contraction begins 4 Myosin cross bridge The aftermath Figure 9.11, step 7

Figure 9.11, step 8 Steps in E-C Coupling: The aftermath Sarcolemma Voltage-sensitive tubule protein T tubule 1 Action potential is propagated along the sarcolemma and down the T tubules. Ca2+ release channel Calcium ions are released. 2 Terminal cisterna of SR Ca2+ Actin Troponin Tropomyosin blocking active sites Ca2+ Myosin Calcium binds to troponin and removes the blocking action of tropomyosin. 3 Active sites exposed and ready for myosin binding Contraction begins 4 Myosin cross bridge The aftermath Figure 9.11, step 8

ATP is needed for this to occur. The thick filaments pull on the thin filaments causing the cell to contract. ATP is needed for this to occur. Thin filament Actin Ca2+ Myosin cross bridge ADP Pi Thick filament Myosin 1 Cross bridge formation. ADP ADP Pi ATP hydrolysis Pi 4 Cocking of myosin head. 2 The power (working) stroke. ATP ATP 3 Cross bridge detachment. Figure 9.12

Cross bridge formation. Actin Ca2+ Thin filament ADP Myosin cross bridge Pi Thick filament Myosin 1 Cross bridge formation. Figure 9.12, step 1

The power (working) stroke. ADP Pi 2 The power (working) stroke. Figure 9.12, step 3

Cross bridge detachment. ATP 3 Cross bridge detachment. Figure 9.12, step 4

ADP ATP hydrolysis Pi 4 Cocking of myosin head. Figure 9.12, step 5

Figure 9.12 Thin filament Actin Ca2+ Myosin cross bridge Thick ADP Pi Thick filament Myosin 1 Cross bridge formation. ADP ADP Pi ATP hydrolysis Pi 4 Cocking of myosin head. 2 The power (working) stroke. ATP ATP 3 Cross bridge detachment. Figure 9.12

Lets look at ATP’s role in the cross-bridge cycle