1. A signal travels down a motor neuron axon to the neuromuscular junction. 2. Vesicles at the axon terminal release acetylcholine into the synaptic cleft. 3. Acetylcholine binds receptor sites on the muscle fiber membrane, causing it to become permeable to sodium ions.

1. Z-line Z-line Actin Myosin Na + Na+ Na+ Na+ Na+ Na+ Na+ Na+ Na+ K + K+ K+ K+ K+ K+ K+ K+ K+ K+ K+ K+ Na+ Na+ Na+ Na+ Na+ Na+ Na+ “ Polarized ” Neuromuscular Junction Neuromuscular Junction at “ Resting Potential ” K+ K+ K+ K+

2. 1. A “ signal ” is sent from the brain down the axon of a motor neuron . “signal” direction Action Potential!!!

4. The question to ask at this point is, what is a depolarization wave ? To explain this we must go back for a moment and look at resting potential and polarization .

5. To maintain resting potential , the sodium-potassium pump (Na + /K + ) pumps out 3 sodium ions (Na + ) for each 2 potassium ions (K + ) pumped into the neuron. This results in more potassium ions inside and more sodium ions on the outside. Outside neuron

6. Unequal pumping ( 3 Na + out to 2 K + in ) results in more positive charge on the outside compared to the inside. The membrane is polarized .

7. Some K + channels are open so K + tends to leak out. This adds to negative charge inside. The charge difference prevents further leakage.

8. When the neuron cell body is stimulated, an electrical impulse is sent down the axon. This impulse is simply the movement of “charged particles” (ions) across a semi-permeable membrane. Think of it as “Sodium in/Sodium out” in its simplest form. “Sodium in” = depolarization “Sodium out” = repolarization

9. Na+ Na+ Na+ Na+ Na+ Na+ K+ K+ K+ K+ K+ K+ K+ K+ K+ K+ K+

10. Na + Na + Na + K+ K+ Na + K + K + K + K + K + K + K + K + K + Na + Na + Na +

11. Na + Na + Na + Na + Na + K + Na + Na + K + K + K + K + K + K + K + K + K + Na + Na + Na +

12. Na + Na + K + K + Na + Na + Na + Na + Na + K + K + K + K + K + Na + Na + Na + K + K + K + K +

13. Na + Na + Na + Na + Na + K + Na + Na + Na + K + K+ K+ K + Na + K + K + K + Na + K+ K+

14. Na + Na + Na + Na + Na + Na + Na + Na+ Na+ K+ K+ Na + K+ K+ K+ K+ K+ K+ K+ K+ K+ K+

15. Na+ Na+ Na+ Na+ Na+ Na+ Na+ K+ K+ K+ K+ K+ K+ K+ K+ Na+ Na+ Na+

16. Na+ Na+ Na+ Na+ Na+ Na+ Na+ K+ K+ K+ K+ K+ K+ K+ K+ Na+ Na+ Na+ K+ K+

17. Na+ Na+ Na+ Na+ Na+ Na+ Na+ Na+ Na+ Na+ K+ K+ K+ K+ K+ K+ K+ K+ K+ K+ K+

18. 2. The signal hits the terminal bud (button) of the axon.

19. 3. The vesicles break open releasing the neurotransmitter , acetylcholine , in to the synaptic cleft .

20. 4. The acetylcholine crosses the synaptic cleft and binds to receptor sites on the sarcolemma .

22. 5. The sarcolemma undergoes a permeability shift from Na + impermeable to Na + permeable .

23. 6. Na + ions rush in to the muscle fiber through channels in the sarcolemma, but they “ overshoot ” equilibrium .

24. 7. Cholinesterase , an enzyme that “ destroys ” acetylcholine, deactivates and removes the acetylcholine from the receptor sites on the sarcolemma.

25. 8. The permeability of the sarcolemma shifts back to Na + impermeable thus trapping the Na + ions inside the muscle fiber.

26. 9. The neuromuscular junction is “ depolarized ” with respect to Na + .

27. Steps 1 through 9, documented as “Action Potential” are actually the steps of depolarization . The depolarization of the neuromuscular junction also means that the sarcolemma of the muscle fiber has been depolarized , with respect to Sodium. The second part of action potential is “ repolarization ” and the steps for this are as follows:

28. 1. K + ions diffuse out of the muscle fiber to help balance the positive charge “imbalance” caused by the Na + being trapped inside the fiber.

29. 2. Na + ions are “pumped” out of the muscle fiber and K + ions are “pumped” back in by the active transport mechanism known as the Na + /K + pump in a ratio of 3 Na + out to 2 K + in . Inside Muscle Fiber Outside muscle fiber

30. 3. Once the original balance of Na + and K + is restored, the NMJ is said to be repolarized . **Please note - This means the Na + is mostly back in the synaptic cleft, outside the muscle fiber, and the K + is on both sides, but more is inside the muscle fiber. Inside muscle fiber

32. The trick here is that depolarization of the N.M.J. is what stimulates the muscle to go through contraction , while repolarization stimulates relaxation . Depolarization of NMJ Contraction Repolarization of NMJ Relaxation

33. However, the timing of these events is as follows: Time in milliseconds 0 x Depolarization of NMJ Repolarization of NMJ Contraction of sarcomere Relaxation of sarcomere

34. Another way of looking at the timing is as follows: Time in milliseconds 0 x Depolarization of NMJ Repolarization of NMJ Contraction of sarcomere Relaxation of sarcomere