Physiology of Synapses in the CNS- L3

1. Physiology of Synapses in the CNS- L3 Faisal I. Mohammed, MD, PhD University of Jordan

2. Objectives Students should be able to: • Define synapse and list the types of synapse • Describe the mechanism of neurotransmitter release • List the major types of neurotransmitters (NT) • Compare the small molecules NT and Neuropeptides • Describe the resting membrane potential and Nernst Equation • Determine the how EPSP, IPSP and Presynaptic inhibition develops • Describe summation of EPSP and IPSP • Describe the characteristics of synapse (Fatigue and Delay) University of Jordan

3. Neurotransmitters University of Jordan

4. Comparison between Small Molecules and Neuropeptides Neurotramsmitters (NT) • Small molecules NT are rapidly acting as compared to slowly acting neuropepides • Small molecules NT are have short lived action compared to prolonged time of action for neuropeptides • Small molecules NT are excreted in larger amounts compared to smaller quantities of neuropeptide • Small molecules NT vesicles are recycled but neuropeptide ones are not • Neuropeptides are co-secreted with small molecules NT • Neuropeptides are synthesized at the soma while small molecules could be formed at the presynaptic terminals University of Jordan

5. Removal of Neurotransmitter • Diffusion • move down concentration gradient • Enzymatic degradation • Acetylcholinesterase for (Ach), peptidases for neuropeptides • Uptake by neurons or glia cells • neurotransmitter transporters • Prozac = serotonin reuptake inhibitor University of Jordan

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8. Electrical Events During Neuronal Excitation • Resting membrane potential ~ -65 mV • Results from the distribution of ions across the neuronal membrane: • Na+ gradient from outside to inside • K+ gradient from inside to outside • Cl- gradient from outside to inside • The movement of the ions down the concentration gradients causes neuronal activation. University of Jordan

9. Nernst Potential • Potential that exactly opposes the movement of an ion across the neuronal membrane. • Nernst Equation: • Electro Motive Force (EMF) (mV) EMF (mV) • The sign is (-) for a positive ion and (+) for a negative ion. University of Jordan

10. A membrane potential of 61mV would be required to prevent the influx of sodium Dendrite X Na+: 142 mEq/L 14 mEq/L K+ : 4.5 mEq/L 120 mEq/L Axon Cl- : 107 mEq/L 8 mEq/L 61mV University of Jordan

11. Dendrite A membrane potential of -87mV would be required to prevent the efflux of potassium Na+: 142 mEq/L 14 mEq/L X K+ : 4.5 mEq/L 120 mEq/L Axon Cl- : 107 mEq/L 8 mEq/L -87mV University of Jordan

12. Dendrite A membrane potential of -69mV would be required to prevent the influx of chloride Na+: 142 mEq/L 14 mEq/L K+ : 4.5 mEq/L 120 mEq/L Axon X Cl- : 107 mEq/L 8 mEq/L -69mV University of Jordan

13. Postsynaptic Potentials • The Excitatory Postsynaptic Potential (EPSP) • Na+ ions rush to inside of membrane through ionophores opened by transmitter. • Rapid influx of positively charged Na+ ions neutralizes part of negativity of the resting membrane potential. • The increase in voltage above the normal resting potential (to a less negative value ~ -45mV) is the excitatory postsynaptic potential. University of Jordan

14. Hyperpolarized/Depolarized Graded Potential University of Jordan

15. Excitory and Inhibitory Postsynaptic Potentials • The effect of a neurotransmitter can be either excitatory or inhibitory • a depolarizing postsynaptic potential is called an EPSP • it results from the opening of ligand-gated Na+ channels • the postsynaptic cell is more likely to reach threshold • an inhibitory postsynaptic potential is called an IPSP • it results from the opening of ligand-gated Cl- or K+ channels • it causes the postsynaptic cell to become more negative or hyperpolarized • the postsynaptic cell is less likely to reach threshold University of Jordan

16. EPSP, increased permeability to sodium causes membrane potential to be less negative Dendrite Na+: 142 mEq/L 14 mEq/L K+ : 4.5 mEq/L 120 mEq/L Axon Cl- : 107 mEq/L 8 mEq/L -45mV University of Jordan

17. Postsynaptic Potentials • The Inhibitory Postsynaptic Potential (IPSP) • Inhibitory synapses open K+ or Cl- channels and causes hyperpolarization of the neuron. • Positively charged K+ ions moving to exterior make membrane potential more negative than normal. • Negatively charged Cl- ions moving to interior make membrane potential more negative than usual. • Increase in negativity beyond the normal resting membrane potential level is the inhibitory postsynaptic potential (IPSP). University of Jordan

18. IPSP, increased permeability to potassium and chloride causes membrane potential to be more negative Dendrite Na+: 142 mEq/L 14 mEq/L K+ : 4.5 mEq/L 120 mEq/L Axon Cl- : 107 mEq/L 8 mEq/L -90mV University of Jordan

19. Inhibition by short circuit: an increase in chloride permeability will balance the depolarization caused by an influx of sodium Dendrite Na+: 142 mEq/L 14 mEq/L K+: 4.5 mEq/L 120 mEq/L Axon Cl-: 107 mEq/L 8 mEq/L -65mV University of Jordan

20. Thank You University of Jordan