1. SYNAPTIC & NEUROMUSCULAR TRANSMISSION Ass. Prof. Dr. Emre Hamurtekin EMU Faculty of Pharmacy

2. INTRODUCTION Axodendritic synapses Axosomatic synapses Axo-axonal synapses

3. INTRODUCTION Each presynaptic terminal of a chemical synapse is seperated from the postsynaptic structure by a synaptic cleft. Postsynaptic density is a thickening located in the postsynaptic structure and a complex of specific receptors, binding proteins and enzymes. Synaptic vesicles: Membrane-enclosed vesicles inside the presynaptic terminal which contain neurotransmitters.  Small, clear synaptic vesicles (Ach, Gly, GABA, glutamate)  Small vesicles with a dense core (catecholamines)  Large vesicles with a dense core (neuropeptides) Ca enters the presynaptic neuron and triggers exocytosis of neurotransmitters.

4. INTRODUCTION

5. EXCITATORY & INHIBITORY POSTSYNAPTIC POTENTIALS A single stimulus produces an initial depolarizing response and after reaching its peak, declines exponentially. During this potential, the excitability of the neuron to other stimuli is increased. This potential is called excitatory postsynaptic potential (EPSP). The excitatory transmitter opens Na or Ca channels in the postsynaptic membrane. Stimulation of some inputs produces hyperpolarizing responses and excitability of the neuron to other stimuli decreases. This potential is called inhibitory postsynaptic potential (IPSP). An IPSP can be produced by a localized increase in Cl transport; negative charge is transferred into the cell. IPSP can also be produced by opening of K channels or closure of Na and Ca channels.

6. EXCITATORY & INHIBITORY POSTSYNAPTIC POTENTIALS

7. TEMPORAL & SPATIAL SUMMATION Temporal summation: If a second EPSP from a single neuron is elicited before the first EPSP decays, the two potentials summate and their additive effects are sufficient to induce an action potential in the postsynaptic membrane. Time constant of the postsynaptic neuron affects the amplitude of the depolarization caused by consecutive EPSPs produced by a single presynaptic neuron. Spatial summation: EPSPs from different presynaptic neurons summate and their additive effects become sufficient to induce an action potential in the postsynaptic membrane. Length constant of the postsynaptic neuron affects the amplitude of the depolarization caused by consecutive EPSPs produced by diffrent presynaptic neurons.

10. INHIBITION AT SYNAPSES Inhibition in the CNS can be;  postsynaptic  presynaptic Postsynaptic inhibition occurs when an inhibitory transmitter (i.e. glycine, GABA) is released from a presynaptic nerve terminal onto the postsynaptic neuron.

11. POSTSYNAPTIC INHIBITION

12. INHIBITION AT SYNAPSES Presynaptic inhibition is a process mediated by neurons whose terminals are on excitatory endings, forming axoaxonal synapses. There are 3 mechanisms for presynaptic inhibition:  Increase in Cl conductance and reduces Ca entry and reduction in the amount of excitatory transmitter release.  Opening of voltage-gated K channels results with K efflux and thus Ca entry decreases.  Direct inhibition of transmitter release independent of Ca influx.

13. GABA is the first transmitter shown to produce presynaptic inhibition.  Increase in Cl conductance (GABA-A receptors)  Increase in K conductance (GABA-B receptors)

14. PRESYNAPTIC FACILITATION The action potential is prolonged and this increases the duration that the Ca channels stay open.

15. NEUROMUSCULAR JUNCTION

16. NEUROMUSCULAR TRANSMISSION 1.The impulse arriving in the end of the motor neuron increases the permeability of its endings to Ca. 2.Ca enters the nerve ending. 3.Ca triggers the exocytosis of acetylcholine-containing synaptic vesicles. 4.Acetylcholine in the synapse binds to nicotinic receptors located in the motor end plate. 5.Binding of Ach to these receptors increases the Na and K conductance. 6.Influx of Na produces a depolarizing potential (end-plate potential) 7.Local potential depolarizes the adjacent muscle plasma membrane and action potential occurs in the muscle membrane. 8.The muscle membrane action potential initiates muscle contraction.

17. THE END