Porth's Essentials of Pathophysiology, 4e

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Organization and Control of Neural Function

C h a p t e r 3 4

Neurotransmitter Removal. Precise control of synaptic function relies on the rapid removal of the neurotransmitter from the receptor site. A released neurotransmitter can (1) be taken back up into the neu- ron through reuptake, (2) diffuse out of the synaptic cleft, or (3) be broken down by enzymes into inac- tive substances or metabolites. The action of norepinephrine is largely terminated by the reuptake process, in which the neurotransmitter is taken back into the neuron in an unchanged form and reused. It can also be broken down by enzymes in the synaptic cleft or in the nerve terminals. The neurotransmitter ace- tylcholine is rapidly broken down by the enzyme acetylcholinesterase. 3

Reuptake

3

1

Metabolite

2

Diffusion

Part of degraded neurotransmitter

Na +

Postsynaptic receptor

Ion channel

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receptors, but bring about long-term changes that subtly enhance or depress the action of the receptors. Neuromodulators, such as dopamine, serotonin, acetyl- choline, histamine, and others, may act at either presyn- aptic or postsynaptic sites. They may act on postsynaptic receptors to produce slower and longer-lasting changes in membrane excitability, by enhancing or decreasing the action of faster-acting neurotransmitter molecules. By combining with autoreceptors on its own presynaptic membrane, a transmitter can act as a neuromodulator by augmenting or inhibiting further nerve activity. In some nerves, such as the peripheral sympathetic nerves, a mes- senger molecule can have both transmitter and modula- tor functions. For example, norepinephrine can activate an α 1 -adrenergic postsynaptic receptor to produce vaso- constriction or stimulate an α 2 -adrenergic presynaptic receptor to inhibit further norepinephrine release. Neurotrophic Factors. Neurotrophic factors, also known as neurotrophins , are a family of polypeptide growth factors that influence the proliferation, differen- tiation, and survival of neuronal and nonneuronal cells. Neurotrophins are secreted by axon terminals indepen- dent of action potentials. Examples include neuron-to- neuron trophic factors in the sequential synapses of CNS sensory neurons. Trophic factors from target cells that enter the axon and are necessary for the long-term sur- vival of presynaptic neurons also have been demonstrated. Alterations in neurotrophin levels have been implicated in neurodegenerative disorders such as Alzheimer disease

and Huntington disease, as well as psychiatric disorders such as depression and substance abuse.

SUMMARY CONCEPTS

■■ Neurons communicate with other neurons and body cells through electrical signals in their membrane called action potentials. Action potentials are divided into three parts: (1) the resting membrane potential, during which the membrane is polarized (positively charged on the outside of the membrane and negatively charged on the inside); (2) the depolarization phase, during which sodium channels open, allowing rapid inflow of the charged sodium ions that generate the electrical impulse; and (3) the repolarization phase, during which the outflow of potassium ions returns the membrane to its resting potential. ■■ Neurotransmission or communication relies on chemical messengers or neurotransmitters, released from the presynaptic neuron, that cross the synaptic cleft and then interact with receptors on the postsynaptic neuron.

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