Neuromuscular transmission

Motor Unit Motor Unit :Motor Unit : is the motor neuron and all the muscle fibers it supplies all of these fibers will have the same type (either fast twitch or slow twitch). When a motor unit is activated

The Neuromuscular junction consists of Axon Terminal : contains around 300,000 vesicles which contain the neurotransmitter acetylcholine (Ach). Synaptic Cleft : 20 – 30 nm ( nanometers ) space between the axon terminal & the muscle cell membrane. It contains the enzyme cholinesterase which can destroy Ach.

Synaptic transmission *** Synapse is the junction between two neurones where electrical activity of one neurone is transmitted to the other

Acetylcholine (1)  Ach is synthesized locally in the cytoplasm of the nerve terminal, from active acetate (acetylcoenzyme A) and choline.  Then it is rapidly absorbed into the synaptic vesicles and stored there.  The synaptic vesicles themselves are made by the Golgi Apparatus in the nerve soma ( cell-body).  Then they are carried by Axoplasmic Transport to the nerve terminal, which contains around 300,000 vesicles.  Each vesicle is then filled with around 10,000 Ach molecules.

Steps involved: AP at the synaptic knob -----» Ca channels open (increase Ca permeability) -----» release of neurotransmitter (NT) from synaptic knob to synaptic cleft -----» NT combines with specific receptors on the other membrane -----» postsynaptic potential -----» AP will result

Neuromuscular transmission

Neuromuscular transmission *** Transmission of impulse from nerve to muscle (neuromuscular junction) Steps: AP at nerve knob -----» increase Ca permeability (Ca inter synaptic knob) -----» release of Acetylcholine (Ach) » Ach combine with receptors on motor end plate -----» Na permeability increase -----» end plate potential develop -----» AP spread on the membrane -----» muscle contraction

Myasthenia gravis autoimmuneneuromuscular disease Muscle weakness Due to circulating antibodies that block acetylcholine receptors at the postsynaptic neuromuscular junction Leading to fluctuating muscle weakness and fatigue.

Acetylcholinesterase inhibitors: neostigmine

Curare Arrow poisons competitively and reversibly inhibiting Acetylcholine receptors found at the neuromuscular junction Anesthesia

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Molecular basis of muscle contraction *** Anatomical consideration: Muscle fibre Sarcomere Myosin (thick filament): Cross-bridge Actin (thin filament) Regulatory protein: (Troponin,Tropomyosin) Actin

Events of muscle contraction: *** Acetylcholine released by motor nerve »»»»» EPP »»»»» depolarization of CM (muscle AP) »»»»» Spread of AP into sarcoplasmic reticulum »»»»»release of Ca into the cytoplasm »»»»» Ca combines with troponin »»»»» troponin pull tropomyosin sideway »»»»» exposing the active site on actin »»»»» myosin heads with ATP on them, attached to actin active site »»»»» Resulting in formation of high energy actin-myosin complex »»»»» activation of ATP ase (on myosin heads) »»»»» energy released, which is used for sliding of actin & myosin

Events of muscle contraction: When a new ATP occupies the vacant site on the myosin head, this triggers detachment of myosin from actin The free myosin swings back to its original position, & attached to another actin, & the cycle repeat its self

Events of muscle contraction: When ca is pumped back into sarcoplasmic reticulum »»»»» ca detached from troponin »»»»» tropomyosin return to its original position »»»»» covering active sit on actin »»»»» prevent formation of cross bridge »»»»» relaxation

Muscle contraction **** 1- simple muscle twitch: The mechanical response (contraction) to single AP (single stimulus) 2- Summation of contraction: Spatial summation: the response of single motor unites are added together to produce a strong muscle contraction Temporal summation: when frequency of stimulation increased (on the same motor unite), the degree of summation increased, producing stronger contraction

Types of muscle contraction: 1- Isometric contraction: No change in muscle length, but increase in muscle tension (e.g. standing) 2- Isotonic contraction: Constant tension, with change in muscle length (e.g. lifting a loud)

ELECTROMYOGRAPHY AND MOTOR NERVE CONDUCTION VELOCITY

28 ELECTROMYOGRAPHY (EMG) It’s a recording of electrical activity of the muscle by inserting needle electrode in the belly of the muscles or by applying the surface electrodes. The potentials recorded on volitional effort are derived from motor units of the muscle, hence known as motor unit potentials (MUPs).

29 Electromyography (EMG) is a technique for evaluating and recording physiologic properties of muscles at rest and while contracting.

30 A motor unit is defined as one motor neuron and all of the muscle fibers it innervates.