1. The Synapse A synapse is the functional connection between a neuron and a second cell. The second cell is also a neuron in CNS. In the PNS, the second cell may be either a neuron or an effector cell within a muscle or gland. Neuron-neuron synapses usually involve a connection between the axon of one neuron and the dendrites, cell body, or axon of a second neuron. In almost all synapses, transmission is in one direction only—from the axon of the first (or presynaptic ) neuron to the second (or postsynaptic ) neuron. 1

2. Synaptic transmission is: 2- Electrical (exceptional). 1- Chemical (neurotransmitters) in most cases. A- Electrical Synapses: Gap Junctions. Adjacent cells that are electrically coupled are joined together by gap junctions. In gap junctions, the membranes of the two cells are separated by only 2 nanometers. Gap junctions are present in cardiac muscle, some smooth muscles, between neurons in the brain Gap junctions can open or close according to need. 2

3. 3 The structure of gap junctions. Gap junctions are water-filled channels through which ions can pass from one cell to another. This permits impulses to be conducted directly from one cell to another. Each gap junction is composed of connexin proteins. Six connexin proteins in one plasma membrane line up with six connexin proteins in the other plasma membrane to form each gap junction.

4. 4 B- Chemical Synapses Transmission across the majority of synapses in the nervous system is one-way and occurs through the release of neurotransmitters from presynaptic axon endings. The presynaptic endings are separated from the postsynaptic cell by a synaptic cleft so narrow (about 10 nm). Release of Neurotransmitter Neurotransmitter within the presynaptic endings are contained within synaptic vesicles. In order for the neurotransmitter vesicles to be released into the synaptic cleft, the vesicle membrane must fuse with the axon membrane in the process of exocytosis. Exocytosis, and the consequent release of neurotransmitter molecules into the synaptic cleft, is triggered by action potentials that stimulate the entry of Ca 2+ into the axon terminal through voltage-gated Ca 2+ channels.

5. 5 When there is a greater frequency of action potentials at the axon terminal, there is a greater entry of Ca 2+, and thus a larger number of synaptic vesicles undergoing exocytosis and releasing neurotransmitter molecules. As a result, a greater frequency of action potentials by the presynaptic axon will result in greater stimulation of the postsynaptic neuron. Action of Neurotransmitter Once the neurotransmitter released, they diffuse rapidly across the synaptic cleft and reach the membrane of the postsynaptic cell. The neurotransmitters then bind to specific receptor proteins that are part of the postsynaptic membrane Binding of the neurotransmitter to its receptor protein causes ion channels to open in the postsynaptic membrane. (chemically regulated channels)

6. 6 The release of neurotransmitter. Steps 1–4 summarize how action potentials stimulate the exocytosis of synaptic vesicles. Action potentials open channels for Ca 2+, which enters the cytoplasm and binds to a sensor protein, believed to be synaptotagmin. Meanwhile, docked vesicles are held to the plasma membrane of the axon terminals by a complex of SNARE proteins. The Ca 2+- sensor protein complex alters the SNARE complex to allow the complete fusion of the synaptic vesicles with the plasma membrane, so that neurotransmitters are released by exocytosis from the axon terminal.

7. 7 The opening of specific channels—particularly those that allow Na + or Ca 2+ to enter the cell—produces depolarization, where the inside of the postsynaptic membrane becomes less negative. This depolarization is called an excitatory postsynaptic potential (EPSP) because the membrane potential moves toward the threshold required for action potentials. when CI − enters the cell through specific channels, a hyperpolarization is produced (where the inside of the postsynaptic membrane becomes more negative). This hyperpolarization is called an inhibitory postsynaptic potential (IPSP) because the membrane potential moves farther from the threshold depolarization required to produce action potentials. Excitatory postsynaptic potentials, stimulate the postsynaptic cell to produce action potentials, and inhibitory postsynaptic potentials antagonize this effect. The EPSPs and IPSPs are produced at the dendrites and must propagate to the initial segment of the axon to influence action potential production.

8. 8 The functional specialization of different regions in a multipolar neuron. Integration of input (EPSPs and IPSPs) generally occurs in the dendrites and cell body, with the axon serving to conduct action potentials.

9. 9 The total depolarization produced by the summation of EPSPs and IPSPs at the initial segment of the axon will determine whether the axon will fire action potentials, and the frequency with which it fires action potentials. Once the first action potentials are produced, they will regenerate themselves along the axon. Events in excitatory synaptic transmission. The different regions of the postsynaptic neuron are specialized, with ligand- (chemically) gated channels located in the dendrites and cell body, and voltage-gated channels located in the axon.

10. 10 Acetylcholine (Ach) neurotransmitter ACh may be either excitatory or inhibitory, depending on the organ involved. The varying responses of postsynaptic cells to the same chemical can be explained, in part, by the fact that different postsynaptic cells have different subtypes of ACh receptors. There are two types of ACh receptors 1. Nicotinic ACh receptors (can also be activated by nicotine). These are found in specific regions of the brain and in skeletal muscle. The release of ACh stimulates muscle contraction. 2. Muscarinic ACh receptors (can also be produced by muscarine __ a drug derived from certain poisonous mushrooms __ ). These are found in the plasma membrane of smooth muscle cells, cardiac muscle cells and the brain.

11. 11 The activation of muscarinic ACh receptors by ACh released is required for the regulation of the cardiovascular system, digestive system, and others. Drugs that activate receptor proteins are called agonists, and drugs that inhibit receptor proteins are antagonists. Muscarine is an agonist of muscarinic ACh receptors, whereas atropine is an antagonist of muscarinic receptors.

12. 12 AChE is present on the postsynaptic membrane or immediately outside the membrane, with its active site facing the synaptic cleft. AChE hydrolyzes acetylcholine into acetate and choline, which can then reenter the presynaptic axon terminals and be resynthesized into acetylcholine (ACh). In order for activity in the postsynaptic cell to be stopped, free ACh must be inactivated very soon after it is released acetylcholinesterase, or AChE enzyme. The ACh-receptor complex quickly dissociates but can be quickly re-formed as long as free ACh is in the vicinity. Acetylcholinesterase (AChE)

13. 13 The action of acetylcholinesterase (AChE). The AChE in the postsynaptic cell membrane inactivates the ACh released into the synaptic cleft. This prevents continued stimulation of the postsynaptic cell unless more ACh is released by the axon. The acetate and choline are taken back into the presynaptic axon and used to resynthesize acetylcholine.

14. 14 Clinical Example Nerve gas exerts its odious effects by inhibiting AChE in skeletal muscles. Since ACh is not degraded, it can continue to combine with receptor proteins and can continue to stimulate the postsynaptic cell, leading to spastic paralysis. Clinically, cholinesterase inhibitors (such as neostigmine) are used to enhance the effects of ACh on muscle contraction when neuromuscular transmission is weak, as in the disease myasthenia gravis.