NEUROMUSCULAR JUNCTION DR. ZAHOOR ALI SHAIKH LECTURE--11 1

NEUROMUSCULAR JUNCTION(N.M.J) Neuromuscular junction is the junction between Motor neuron and Skeletal muscle fiber. They are linked chemically. Neurotransmitter at neuromuscular junction is Acetylcholine. 2

N.M.JUNCTION [CONT] Anatomy & Physiology REMEMBER - Motor axon - Axon terminal - Terminal button - Vesicles (present in terminal button) having Neurotransmitter Acetylcholine - Cleft or Space - Motor end plate (Muscle cell membrane) 3

N. M. JUNCTION [cont] An Action potential is propagated in a motor neuron, along its large myelinated axon (efferent nerve fiber), to the skeletal muscle fiber. As the axon approaches the muscle, it gives axon terminals and loses its myelin sheath. 4

N. M. JUNCTION [cont] Each of the axon terminal forms a special junction with a muscle fiber called Neuromuscular Junction. (one axon terminal innervates only one muscle fiber) therefore one muscle cell has one neuromuscular junction. Axon terminal branch ends in a enlarged knob like structure called Terminal button. Vesicles which contain chemical transmitter are present in terminal button. 5

N. M. JUNCTION [cont] Axon terminal fits in the underlying muscle fiber. This portion of muscle cell membrane is called MOTOR END PLATE. There is Space or Cleft between axon terminal and motor end plate. 6

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N. M. JUNCTION [cont] Events at a Neuromuscular Junction 1) An action potential in a motor neuron is propagated to the axon terminal (terminal button). 2) This local AP at the axon terminal causes the opening of Ca2+ channels and therefore Ca2+ entry into the terminal button. 9

N. M. JUNCTION [cont] 3) Ca2+ triggers the release of acetylcholine (ACh) by exocytosis from the vesicles. 4) ACh diffuses across the space between the nerve and muscle cells and binds with RECEPTORS on motor end plate of the muscle membrane 5) This binding causes opening of Na+ channels and Na+ entry into muscle cell. 10

N. M. JUNCTION [cont] 6) Na+ entry causes depolarization of Motor end plate called END PLATE POTENTIAL ( EPP). 7) The resultant Na+ entry initiates action- potential in the muscle fiber. 8) Acetylcholine is destroyed by enzyme acetylcholinesterase. This enzyme is located on the motor end plate membrane. Destruction of ACh, causes termination of the muscle cell response. 11

N. M. JUNCTION [cont] IMPORTANT Remember the name of enzyme which destroys Acetylcholine (ACh). It is called Acetylcholinesterase (AChE). It is located in the Motor end plate (Muscle membrane). 12

13 Neuromuscular Junction

MYASTHENIA GRAVIS Myasthenia gravis is a disease of Neuromuscular junction.  Q- What causes Myasthenia gravis ? A- Myasthenia gravis is caused by ANTIBODIES produced against Acetylcholine receptors. It is an Autoimmune disease. Autoimmune means immunity against self. It is more common in young females than males. 14

MYASTHENIA GRAVIS [cont] In Myasthenia gravis, body by mistake produces antibodies against its own motor end-plate acetylcholine receptor channels.  What does patient complain ? Patient complains of muscle weakness. (myasthenia means “muscle weakness”, gravis means “severe”). Patient can not go up stairs. 15

MYASTHENIA GRAVIS [cont] Patient complaints (cont) Ptosis (dropping of eyelids). In sever cases difficulty in breathing.  Q- What treatment is given? Drug such as Neostigmine that inhibits enzyme AChE (Acetylcholinestrase) is given. This drug prolongs the action of acetylcholine at neuromuscular junction. 16

EFFECTS OF CHEMICAL AGENTS AT N.M.JUNCTION  CURARE Curare blocks Ach receptors channels on motor end plate, muscle membrane. Therefore acetylcholine can not act to open the Na+ channels. Muscle action potential can not occur in response to nerve impulses. 17

EFFECTS OF CHEMICAL AGENTS AT N.M.JUNCTION CURARE [cont] Curare causes muscle relaxation. In high dose, Muscle paralysis can occur. If more curare given it can cause Respiratory muscle (Diaphragm) paralysis and death. 18

SYNAPSE AND NEUROMUSCULAR JUNCTION ‘SIMILARITIES’ Both synapse and neuromuscular junction have cleft (space) therefore no direct transmission of electrical activity. Chemical neurotransmitter is released by Ca2+ in both. Neurotransmitter acts on receptors to open Na+ channels. 19

SYNAPSE AND NEUROMUSCULAR JUNCTION ‘DIFFERENCES’ Synapse is junction between two neurons but neuromuscular junction is present between motor neuron and skeletal muscle fiber. Neuromuscular junction is always excitatory, End Plate Potential (EPP). But Synapse may be either excitatory (EPSP) or Inhibitory (IPSP). 20

Thank you 21