In the early twentieth century, physiologists were still unsure how nerve cells communicated with one another. Some thought electrical impulses “jumped the gap” from one neuron to another or from neurons to the cells of a target organ such as a muscle. Alternatively, the terminal might release a chemical substance that acted on the receiving cell. Some indirect evidence supported this chemical hypothesis of nerve cell communication, but no one had yet performed a definitive experiment testing the hypothesis.
This brings us to Otto Loewi, a German pharmacologist who carried out the long-awaited experiment in 1920. Loewi later recounted that the idea of chemical transmission had occurred to him as early as 1903, but at that time he had no way of testing the idea and thus forgot about it for many years. Meanwhile, he had begun studying the control of the frog heart by the vagus nerve, a parasympathetic nerve that reduces heart rate. In Loewi’s own words:
The night before Easter Sunday of that year (1920) I awoke, turned on the light, and jotted down a few notes on a tiny slip of thin paper. Then I fell asleep again. It occurred to me at six o’clock in the morning that during the night I had written down something most important, but I was unable to decipher the scrawl. The next night, at three o’clock, the idea returned.
It was the design of an experiment to determine whether or not the hypothesis of chemical transmission I had uttered seventeen years ago was correct. I got up immediately, went to the laboratory, and performed a simple experiment on a frog heart according to the nocturnal design. (Loewi, 1960, p. 17)
In his “simple experiment,” Loewi first removed the hearts of two frogs, only one of which still had the vagus nerve attached, and bathed the organs in a solution that would keep them functioning for a while. The vagus nerve of the first heart was electrically stimulated, which caused the heart to slow down as expected. The fluid that had been bathing the first heart was then transferred to the second heart, and, amazingly, the second heart slowed down as well. This meant that stimulation of the vagus nerve released a chemical substance that was responsible for the decrease in heart rate. Loewi named this unknown chemical Vagusstoff (“vagus material”), and within a few years it was identified as the substance acetylcholine (ACh). Interestingly, Loewi admitted that if he had carefully considered this experiment in the daytime instead of rushing to the lab in the middle of the night, he would have rejected it as being unlikely to succeed. For example, even if a chemical is released from the nerve, it might be in quantities too small to affect the recipient heart. Fortunately, Loewi had some luck on his side (in addition to his insight): not only did the vagus nerve liberate enough ACh to affect the recipient heart, but the neurotransmitter was able to persist in the transferred fluid because the frog heart has a lower capacity to break down ACh than the hearts of many other species.
Loewi’s experiment introduces one of the body’s great systems, cellular communication, the system of synaptic transmission. In the rest of this chapter, you will learn more about synapses, neurotransmitters, and the mechanisms of neurotransmitter action. The final section is devoted to a second important communication system, the endocrine system, which is responsible for secretion of hormones into the bloodstream.( The third great signaling system is the immune system, discussion of which is beyond the scope of this text.)