XL. Intercellular Nerve Conduction: Synapse

neuronal computer: wires and chips

Complex regulation of synaptic transmission allows for complexity of responses: whereas AP transmission can be likened to electrical transmission through wires, synapses are the “computer chips” of the nervous system.

railway junction

Action potentials transmitted along the length of the neuron must travel to other neurons too. The AP transmission to another cell takes place at the contact point between the end of the axon of one cell and the soma or dendrite of another cell.

These intercellular contacts are called synapses. There are two main kinds of synapses: electrical and chemical.

In electrical synapses, the adjacent cells are joined by gap junctions. Cytoplasm is continuous across these junctions, and the ionic imbalance spreads quickly from one cell to another.

In chemical synapses, adjacent cells are not physically connected. The information travels by means of a chemical intermediate from one cell to another.

Structure of a Chemical Synapse

presynaptic, postsynaptic membranes and neurotransmitters

The end of an axon contains vesicles packed with chemical neurotransmitters.

The membrane of the axon (presynaptic membrane) is separated by the synaptic cleft, a space 20 nm wide, from the postsynaptic membrane of the dendrite or soma of another neuron.

The postsynaptic membrane contains receptors for neurotransmitters.

Mechanism of Synaptic Transmission

APàCa channelsàfusion of synaptic vesiclesàNT diffusion accross the cleftà binding to receptorsà graded potential

An action potential arrives at the presynaptic membrane;

voltage-gated Ca channels open;

Ca flows into the presynaptic neuron (there is 100,000 times more Ca in the intercellular space);

Ca stimulates fusion of synaptic vesicles with the presynaptic membrane;

as many as 10,000 molecules of neurotransmitter are released into the synaptic cleft;

neurotransmitters diffuse across the synaptic cleft;

neurotransmitters bind to receptors of the postsynaptic membrane;

binding of neurotransmitters to their receptors opens ion channels in the postsynaptic membrane;

the resting potential of the postsynaptic membrane is perturbed, generating graded potential;

Excitatory and inhibitory postsynaptic potentials

some synapses are excitatory (i.e. when opened, Na channels depolarize postsynaptic membrane and start AP), they create excitatory postsynaptic potential (EPSP);

some synapses are inhibitory (open K channels hyperpolarize the membrane), generating inhibitory postsynaptic potential (IPSP);

an enzyme, acetylcholine esterase, breaks down the neurotransmitters in the cleft.

Whether the synapse is excitatory or inhibitory is determined by the kind of the neurotransmitter receptors and not the neurotransmitter itself. For example acetocholine is excitatory at the neuro-muscular junction of skeletal muscle but inhibitory in heart muscle.

EPSP and IPSP of the postsynaptic membrane are summed, and if the threshold is reached. action potential is generated in the postsynaptic neuron. Note that triggering of AP thus depends on the number of excitatory and inhibitory synapses and their distance from the hillock of the postsynaptic neuron.

Synapses do not respond to the same stimulus in a precisely defined way, they display plasticity. Depending on the frequency and the intensity of the stimulus, the sensitivity of the same synapse changes with time. Cyclic AMP released in the postsynaptic neuron changes the response of receptors to given neurotransmitters.

Neurotransmitters

A variety of compounds act as neurotransmitters.

Some are simple organic chemicals:

Acth - brain and body

dopamine, serotonin, GABA - brain only

enkephalins, endorphins - brain (emotion)

acetylcholine and norepinephrine are found in the synapses of the central nervous system and the body;

dopamine, serotonin, GABA, and glutamic acid are found only in the central nervous system;

some are peptides 2-40 amino acids long:

short ones are called enkephalins and longer ones endorphins. They are found in the brain synapses in the regions of the brain controlling emotion and pain. Morphine, which mimics endorphins, affects these responses.

Drugs

fried brain synapses:
synthesis of NT
uptake of NT: Reserpine
release into cleft
mimicry: nicotine, cocaine, LSD
degradation of NT: speed

Synaptic transmission is a complex pathway involving a variety of proteins and ligands and transmission can be modified a number of ways. For example:

synthesis of neurotransmitter can be inhibited;

uptake of neurotransmitter into synaptic vesicles can be blocked (Reserpineâ, a sedative, does this);

release of neurotransmitters into the cleft can be inhibited;

different compounds can mimic neurotransmitter and compete for receptor, e.g. nicotine mimics acetocholine; cocaine blocks the Na channel; LSD blocks serotonin receptors, Valium acts synergistically with GABA to open Cl channels and prevent transmission; opiates bind to receptors in the brain and block transmission of pain; Demerol, codeine, and methadone act similarly;

degradation of neurotransmitters can be blocked; amphetamines (Benzedrine, Dexedrine, “speed”) work this way.

Some diseases are related to modulation of the synaptic transmission.

Parkinson’s: no dopamine
Alzheimer’s: no Acth

In Parkinson's disease, neurons producing dopamine die; Alzheimer's disease is accompanied by the death of neurons producing acetocholine.