New Chapt 11-criteria for neurotransmitters�(1)

New Chapt 11-criteria for neurotransmitters�(1) -...

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Unformatted text preview: 113 CHAPTER 11 CHEMICAL SYNAPTIC TRANSMISSION THE CRITERIA FOR TRANSMITTERS The last chapter presented an introduction to chemical synaptic transmission. In this chapter, we take a look at the variety of chemical substances which can act as neurotransmitters at synapses and examine, in greater detail, how a transmitter produces a synaptic potential in the postsynaptic target cell. The discovery of acetylcholine The first neurotransmitter to be identified was acetylcholine. The story of the identification of this amine as a neurotransmitter begins in 1921 with the work of Otto Loewi. Indeed, how Loewi came to conduct his now famous experiment is a most charming story and is part of the folklore of neuroscience. Loewi was interested in how stimulation of the vagus nerve (a part of the autonomic nervous system) produced a slowing of the heart rate. The great question of the day was between two alternative explanations of how the vagus influenced the heart. One explanation was that the action potential from the nerve was conducted directly into the heart muscle and the injected current slowed the heart down. The alternative explanation was that when the action potential reached the terminal, it released a chemical, and the chemical then somehow influenced the heart and slowed it down. It was unclear how to devise a test that could distinguish between the two explanations. But one night, according to the story, Loewi had a dream in which he conducted the definitive experiment. When he awoke, however, he had completely forgotten how to conduct the experiment. The next night the dream reoccurred, but this time he woke up and wrote down the experiment so that he would be sure to have it in the morning. The next day he conducted his now famous experiment, which showed for the first time that nerves communicate with other cells by chemical transmission. The experiment Loewi conducted is shown in Fig. 1. What he did was to isolate two frog hearts and place each in a different container filled with Ringers solution. Heart 1 was placed in container 1, and heart 2 in container 2. The vagus nerve in heart 1 was intact and its heart rate was slowed when the vagus nerve was stimulated, as illustrated in the right panel of Fig. 1. The fluids in container 1 flowed into container 2 through a tube that connected the two containers. The key result was that a few moments after vagal stimulation slowed heart 1, the heart rate of the heart 2 also slowed. Clearly 114 stimulation of the vagus to the first heart caused the release of some substance into the surrounding fluid which when it reached the second heart produced the slowing of its rate. Loewi named this substance "vagusstoff" (i.e. vagus substance). It was not however until 1936 that the chemical identity of vagusstoff became known. Henry Dale, an English physiologist and a good friend of Loewi, showed that vagusstoff was acetylcholine. Dale confirmed Loewis experiment and made the discovery that when the nerves to skeletal muscles were stimulated, the endings of the motor axons...
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New Chapt 11-criteria for neurotransmitters�(1) -...

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