Physiology Lecture l11 PDF

Physiology Cholinergic Transmission LECTURE (10) DR. El-Sawy 0  Physiology Cholinergic Transmission Def :...

Physiology Cholinergic Transmission LECTURE (10) DR. El-Sawy 0  Physiology Cholinergic Transmission Def :  Functional connection between a neuron and second cell (neuron or muscle or glands) structure : Pre-synaptic  Transmits impulse towards the synapse  10-30 nm. Synaptic cleft  Is full of interstitial fluid.  Separates nerve ending from next neuron or effector organ. Post-synaptic  Transmits impulse away from the synapse. DR. El-Sawy 1  Physiology Cholinergic Transmission Types of synape: Electrical synapse Chemical synapse  Gap junction () presynaptic  Junction () presynaptic & Def & postsynaptic membrane. postsynaptic membrane which is chemically mediated. Presence  Rare  Very common  Chemical substance is  Allows direct transmission of released at nerve endings electrical depolarization Mechanism allowing transmission of waves from presynaptic to nerve impulses from one postsynaptic neuron. neuron to another neuron Fatigue  Resist fatigue  Show fatigue Conduction  Both directions  One direction Speed  Faster  Slower 1. Acetylcholine → Cholinergic transmission. Types 2. Noradrenaline → Adrenergic transmission. DR. El-Sawy 2  Physiology Cholinergic Transmission Site of release : 1) All Pre-ganglionic fibers 2) Sympathetic Pre-ganglionic fibers to adrenal medulla 3) All parasympathetic Post-ganglionic fibers 4) Sympathetic Post-ganglionic fibers to :  Sweat glands.  Skeletal ms blood vessels. 5) Motor end plate ( Neuro-Muscular Junction ) 6) Some synapses in CNS. Synthesis :  Reaction between acetyl co-A and choline in presence of choline – acetyl transferase (CAT) enzyme  Acetyl co-A + choline → acetylcholine + co-A.  ATP and glucose are required to form acetyl CoA. DR. El-Sawy 3  Physiology Cholinergic Transmission Storage :  Stored in nerve terminals in minute vesicles. Each vesicle contains > one thousand Ach molecules (5000-10,000)  Some molecules are found free in the cytoplasm. Release :  When action potential reaches axon terminal  Depolarization  ↑ permeability to Ca ions  Ca influx.  Ca binds to the vesicles & move them towards the membrane where they rupture and release the chemical transmitter inside the synaptic cleft by exocytosis.  Chemical transmitter then passes through the cleft & binds to its receptors on postsynaptic membrane. DR. El-Sawy 4  Physiology Cholinergic Transmission Mechanism of action :  Acetyl Choline binds to receptors on postsynaptic membrane :  Na and Ca influx → Depolarization (stimulation ) Ligand-gated ion channels  K efflux and Cl influx → Hyper-polarization (inhibition).  activates membrane enzymes such as adenyl cyclase → G-protein coupled formation of 2nd messenger called cyclic AMP from ATP → receptors intraceullar signal Removal of acetylcholine : Diffusion  To the surrounding →↓ Ach concentration.  By choline - estrase enzyme. Acetylcholine → acetic acid + choline 1. Choline has a similar action to acetylcholine but weaker Hydrolysis & choline base is reuptaken back into nerve ending to be recycled to form new acetylcholine. 2. Acetate ion diffuse into blood. Reuptake  Not yet definite. DR. El-Sawy 5  Physiology Cholinergic Transmission Clinical Cholinesterases:  Keep action of acetylcholine localized in site of liberation.  Prevent its diffusion to blood causing generalized parasympathetic effects. Anticholinesterases:  Neostigmine  block the action of cholinesterase.  Prolong action of Ach.  Used to treatment of some diseases such as myasthenia gravis. Action of Ach : Muscarinic action Nicotinic action  Muscarine is an alkaloid,  Nicotine which is derived Similar to derived from poisonous from Tobacco action of Mushroom  On smooth ms and glands  Autonomic ganglia supplied by parasymp and  Neuromuscular junction Site symp cholinergic nerve fibers.  Adrenal medulla (secretion of adrenaline & noradrenaline) Onset  Slow  Rapid Duration  Prolonged  Short  Atropine  Ganglion and neuromuscular Antagonist blockers DR. El-Sawy 6  Physiology Cholinergic Transmission Acetylcholine receptors (cholinergic receptors) : Muscarinic Nicotinic Nature  Ligand gated ion channel  G-protein coupled receptors  Effector organs at all  Autonomic ganglia Site postganglionic cholinergic  Adrenal medulla nerve terminals  Motor end plate  M1 → Brain & autonomic 1) Neural nicotinic (Nn) ganglia  Autonomic ganglia  M2 → Heart  Adrenal medulla Sub-types  M3 → Smooth muscles & 2) Muscle nicotinic (Nm) secretory glands.  Motor end plate  M4 → Pancreas  M5 → Under investigation Stimulated  Muscarine  Nicotine (small dose) by Blocked by  Atropine  Nicotine (Large dose) DR. El-Sawy 7