NEUROMUSCULAR TRANSMISSION: sYNAPSE: ~ is the junction between 2 cells where the impulse is transmitted from one cell to another

~ Presynaptic cell (before synapse) & Postsynaptic cell (after synapse) are foun d between: => a neuron and an effector cell 2 types : i) Chemical ~ presynaptic cell exocytoses neurotransmitter onto postsynaptic cell ~ distance btw pre & postsynaptic cell membranes is 3.5nm ~ there is a continuity bte pre & postsynaptic membranes ~ ultrastructural component is Gap-junction channels ~ ion current is the agent of transmission ~ synaptic delay is virtually absent ~ direction of transmission is bidirectional ii) Electrical ~ presynaptic cell is joined to the postsynaptic cell by gap junctions ~ distance btw pre & postsynaptic cell membranes is 20-40nm ~ there is a NO continuity bte pre & postsynaptic membranes ~ ultrastructural component is PRESYNAPTIC VESICLES & ACTIVE ZONES; POSTSYNAPTIC RECEPTORS ~ CHEMICAL TRANSMITTER is the agent of transmission ~ synaptic delay is AT LEAST 0.3ms ~ direction of transmission is UNIDIRECTIONAL Composed of 3 parts: A. axonal termini of the presynaptic neuron ~ contains synaptic vesicles filled with a neurotransmitter B. receptor region on the postsynaptic cell which contains ligand-gated channels ~ when the neurotransmitter binds to the extracellular portion of the channel it opens C. fluid-filled space between the cells (synaptic cleft) ~ separates the presynaptic and postsynaptic cells *The nerves that innervate muscle fibers are called motor neurons EVENTS AT NMJ : 1. action potential arrives at the axon terminus of the presynaptic cell 2. causes the opening of voltage-gated Ca2+ channels. 3. Ca2+ diffuse into the cytoplasm of the axon terminus 4. triggers the fusion of synaptic vesicles with the cell membrane 5. and the exocytosis of neurotransmitters into the synaptic cleft. 6. ACh diffuses across the synaptic cleft 7. binds to nicotinic receptor on the motor end plate 8. Binding of 2 ACh molecules to nicotinic receptor causes cations (mainly Na+) to move into the cell rather than K+ move out of the cell 9. Increased Na+ conductance at motor end plate. 10. resulting in end plate potential

11. Na 12. 13. 14.

Generation of EPP at the motor end plate stimulates opening of voltage-gated channels leading to generation of muscle AP propagation of muscle action potential in muscle plasma membrane ACh breaksdown by aectylcholineesterase

FATE OF NEUROTRANSMITTERS FOLLOWING SYNAPTIC TRANSMISSION: => rapid removal of the acetylcholine prevents continued muscle re-excitation af ter the muscle fiber has recovered from its initial action potential. => ACh removed rapidly by: i. Small amount diffuses away from the synaptic cleft ii. Mostly hydrolyzed by acetylcholinesterase in the synaptic cleft ~ ACh is hydrolyzed into acetate and choline ~ Choline is reuptake back into the presynaptic cell CHARACTERISTIC OF EPP: ~ Each nerve impulse release about 60 ACh vesicles (each contain 10,000 ACh mole cules) can result in 10x impulse transmission across NMJ! ~ EPP is local depolarization, spreads passively to the nearby muscle fiber memb rane ~ EPP serves as the stimulus for a muscle action potential to be initiated. ~ EPP lasts approximately 5-10 msec. ~ EPP amplitude is 25-30 mV NEUROMUSCULAR BLOCKERS: A. Inhibiting ACh synthesis- block choline reuptake e.g. hemicholinum & triethyl choline B. Inhibiting ACh release - e.g. botulinum toxins, excess Mg, aminoglycosides an tibiotics C. Interfering with the postsynaptic action of ACh bind to ACh receptor and bloc k the binding of ACh. e.g. curare & gallamine (pure antagonists) D. Drugs that stimulate the muscle fiber by ACh-like action : ~ Methacholine, carbachol, nicotine F. Drugs that stimulate the neuromuscular junction by inactivating AChE : ~ Neostigmine, physostigmine, diisopropyl fluorophosphate