Seventh lecture

Changes occurring in the nerve as a result of conduction of a nerve impulse: I- Electrical changes

II- Excitability changes It passes in the following phases: a- Temporal rise of excitability is associated with the local b- Absolute refractory period (ARP) c- Relative refractory period (RRP) During this period the excitability of the nerve is partially recovered. Stronger stimuli are needed to excite the nerve. During this period, the gates of K+ channels are opened and the membrane is in the process of depolarization. The magnitude of the second action potential is less than normal. d- Supernormal phase of excitability The excitability is above normal i.e. weaker stimuli can excite the nerve fibers. e- Subnormal phase of excitability: The excitability is below normal i.e. stronger stimuli are needed to excite the nerve fibers.

The nerve contains the enzymes responsible for glycolysis, citric acid (Kreb’s) cycle and electron transport (cytochrome oxidase). Thus the nerve can generate and store energy in the form of ATP. 1- Initial heat. 2- Delayed heat. III- Metabolic changes IV- Thermal changes

Factors affecting the excitability and conductivity of the nerve fibers 1- Physical factors Thermal: Warming increases while cooling decreases the excitability by decreasing the metabolic reac tions need for the Na – K pump. Inhibition of Na-K pump leads to accumulation of the Na+ ions inside the nerve fibers which decreases the membrane potential and lastly leads to loss of the resting membrane potential i.e. loss of excitability and conductivity. Mechanical: Deep pressure on the nerve fibers decreases the excitability and conductivity of these fibers.

2- Chemical factors Local anaesthetic drug as cocaine, novocaine & xylocaine decrease the membrane permeability to Na+ ions (by blocking the Na+ channels). Thus, depolarization is inhibited and consequently the nerve impulse fail to be generated and conducted. Ions Ca++ ions: 1-Increased Ca++ ions decreases excitability of the nerve fibers by decreasing the membrane permeability to Na+ ions and increasing the threshold of stimulation. 2-Decreased Ca++ ions increases excitability by increasing Na+ permeability and decreasing the threshold of stimulation.

Na+ ions: 1-Increased Na+ ions increases excitability by facilitating the process of depolarization. 2-Decreased Na+ ions decreases excitability by delaying the process of depolarization. K+ ions: -Increased K+ ions in the extracellular fluid increases excitability becusae K+ ions diffuse inside the nerve fiber producing depolarization (like Na+ ions). -Decreased K+ ions in the extracellular fluid decreases excitability because K+ ions diffuse from inside to outside the nerve fibers producing hyperpolarization. O2 lack and CO2 excess decreases excitability. H+ ion concentration: Alkalinity increases, while acidity decreases excitability.

3- Electrical factors In electrotonus electrotonic potential, the anelectrotonus decreases while the catelectrotonous increases the excitability.

Nerve block It means failure of conduction of nerve impulses from one place to another. It also means failure of excitability of the nerve fibers i.e. there is no generation or propagation of nerve impulses. Nerve block can be produced by: 1- Physical causes: a-Thermal: Sever cooling. b-Mechanical: Deep pressure. c-Injury or crushing of the nerve fibers. 2- Chemical causes (membrane stabilizers): a-Local anaesthetic drugs. b-Increased Ca++ ions. c-Decreased Na+ ions. d-Decreased K+ ions. 3- Electrical causes: Strong anelectrotonus.

Neuro-musclular junction Since the number of fibers in the muscle greatly exceeds, the number of fibers in the motor nerve. Each nerve fiber branches many times and stimulates a variable number of muscle fibers. A single motor neuron innervates many muscle fibers. A motor neuron, plus the muscle fibers supplied by a motor unit which perform fine and delicate movements, a few muscle fibers are supplied by one motor neuron While in muscles used for rapid coarse movements, many muscle fibers are supplied by a single neuron.

The nerve ending makes a junction called the neuromuscular junction.

Physiological anatomy of the neuro- muscular junction Near the surface of the muscle, the motor nerve fiber loses its myelin sheath and divides into many branches, each branch forms a junction with a single muscle fiber. The terminal part of the axon lies in a shallow groove on the surface of the muscle fiber. The axon terminal contains small vesicles that carry acetylcholine which is the chemical transmitter at the neuromuscular junctions.

The presynaptic terminals contain a large number of mitochondria. The terminal part of the axon is separated from the muscle plasma membrane by a space known as the synaptic cleft. The post-synaptic membrane is the plasma membrane of the muscle fiber. It is called the motor end plate. The surface area of this membrane is greatly increased by the presence of numerous folds of the membrane called the junctional folds. The post-synaptic membrane contain the receptors for the chemical transmitter acetylcholine (cholinergic receptors). These receptors are complex protein molecules that have a double functions. Each receptor has: (1)binding site for acehylcholine (2) an ion channel. The membrane of the motor end plate contains also an enzyme called cholinestrase. This enzyme is essential for breaking down the acetylcholine to an inactive form once it has done its action.

Mechanism of neuro-muscular transmission When nerve impulse in a motor neuron reaches the axon terminal, it opens the voltage sensitive Ca++ channels, and thus allowing the Ca++ ions to diffuse into the axon terminal. The increase in the intracellular Ca++ ion causes the synaptic vesicles that contain acetylcholine to move towards the membrane, fuse with it, and lastly to rupture and release its content into the synaptic cleft. Acetylcholine diffuses across the cleft to the postsynaptic membrane, where it combines with the specific binding sites on the receptor. When the binding occurs, the membrane channels becomes permeable to both Na+ and K+ ions at the same time. Because of the differences in electrochemical gradients across the membrane, more Na+ move in, than K+ moves out, producing a local depolarization of motor end plate known as the motor end plate potential.

The end plate potential causes small local currents which depolarize the adjacent muscle plasma membrane to the threshold level for generation of an action potential. This action potential propagates on both sides of the motor end plate to the whole length of the muscle fiber leading to its contraction. After passage of the action potential, the muscle membrane repolarizes and returns to its resting potential.