Biochemistry of Neurotransmission

Nerve signals must be transmitted not only within a neuron, but also from one neuron to another or to a muscle or gland cell. Transmission within a nerve cell was discussed here. Cell to cell transmission is discussed as follows:

The Cholinergic Synapse - Neurotransmission usually involves release of a chemical messenger, called the neurotransmitter, from the presynaptic cell followed by its binding to receptors on the postsynaptic cell (nerve, muscle, or gland). Synapses involving acetylcholine as the neurotransmitter are called cholinergic synapses. Choline is synthesized principally as part of phosphatidylcholine. A cholinergic synapse is shown in Figure 21.33. Signals move as follows:

> The nerve impulse (action potential) moves down the presynaptic axon to the terminal bulb; the change in membrane potential in the bulb causes the opening of voltage-gated calcium channels, allowing Ca2+ ions to pass from the surrounding space into the axonal bulb (Figure 21.33a).

> Within the bulb are synaptic vesicles, each containing about 10 3 to 10 4 acetylcholine molecules. The increase in Ca 2+ concentration causes these vesicles to fuse with the axonal membrane and open, spilling their contents into the synaptic cleft (Figure 21.33b).

> The postsynaptic membrane of the receptor dendrite has specific acetylcholine receptors, toward which the neurotransmitter diffuses (Figure 21.33c).

> Binding of acetylcholine triggers the opening of ion channels in the postsynaptic membrane (Figure 21.33d), initiating an action potential that can be passed on to the next axon (Figure 21.33e). The action potential involves a wave of membrane permeability changes that lead to sodium influx and potassium efflux.

The receptors here are referred to as nicotinic acetylcholine receptors, because they can bind the alkaloid nicotine. The other major type of acetylcholine receptor, which participates in different synapses, is called the muscarinic acetylcholine receptor.

Acetylcholine is synthesized by choline acetyltransferase from choline and acetyl-CoA in the axonal terminal bulbs. After acetylcholine has been released from vesicles and bound to the receptors, the neurotransmitter is rapidly hydrolyzed by the enzyme acetylcholinesterase, to yield choline, which binds poorly to acetylcholine receptors. Degradation of acetylcholine restores the resting potential in the postsynaptic membrane.

To ready the synapse for another impulse (which must occur about 1000 times per second), the empty synaptic vesicles, which are returned to the axonal terminal bulb by endocytosis, must be refilled with acetylcholine. This task is accomplished by an acetylcholine transporter protein, which brings newly synthesized acetylcholine into the vesicles by exchanging it for protons. As the protons are returned to the cytosol from the vesicles, acetylcholine is transported in the opposite direction.

Nicotinic acetylcholine receptor - Figure 21.34 shows the nicotinic acetylcholine receptor. The central pore is a gated ion channel. Post synaptic membranes are packed densely with receptors (20,000 per square micrometer). Electric organs of electric rays and electric eels contain stacks of cells called electroplaques, with a density of 105 receptors per square micrometer.

Acetylcholinesterase, the enzyme that hydrolyzes acetylcholine to choline in the postsynaptic membrane, is a serine esterase inhibited by diisopropyl fluorophosphate, sarin, physostigmine, and parathion (Table 11.4). These substances are extremely toxic and cause paralysis. Other toxins block the acetylcholine receptor (antagonists) or lock it open (agonists). Nicotine is an agonist.

Adrenergic Receptor - Another kind of synapse uses catecholamines instead of acetylcholine and is called adrenergic. Catecholamines include dopamine, norepinephrine, and epinephrine. In patients with Parkinsonism, dopamine levels are abnormally low in a particular area of the brain. Dopamine does not cross the blood-brain barrier, however, so patients do not respond to treatment with dopamine. Dopa, on the other hand, a precursor of dopamine, does cross the barrier, giving relief to many individuals with Parkinsonism. Dopaminergic neurons (neurons secreting dopamine) may be involved in schizophrenia. In this case, the neurons secrete too much dopamine.

See also: Neurotransmitters and Receptors, Neurotransmitters and Biological Regulators

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