The experiment designed in Otto Loewi’s dream: synaptic signaling used chemical messengers
(by Haohao Wu, 16/12/2013)

Charles Scott Sherrington

Sir Henry Hallett Dale
(1875 - 1968)

Otto Loewi

Otto Loewi
(1873 - 1961)

It was proposed by Santiago Ramón y Cajal, the 1906 Nobel laureate, that the neurons are not continuous even though they communicate with each other. This idea waslater known as neuron doctrine.The neurons are discrete entities with gaps between them and this gap was termed "synapses" by Charles Scott Sherrington.What is the nature of synapse and how impulses transmit across it? The common held belief at that time was that the synaptic transmission is electrical. However, Otto Loewi, a German-born pharmacologist, thought that the signaling through synapses was chemical but he didn’t know how to prove until seventeen years later in 1921 when an important dream occurred to him.

"The night before Easter Sunday of that year I awoke, turned on the light, and jotted down a few notes on a tiny slip of paper. Then I fell asleep again. It occurred to me at 6 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 3 o'clock, the idea returned. It was the design of an experiment to determine whether or not the hypothesis of chemical transmission that I had uttered 17 years ago was correct. I got up immediately, went to the laboratory, and performed a single experiment on a frog's heart according to the nocturnal design."

What Loewi had done on that early morning was to dissect two beating hearts from frogs, one with vagus nerve attached and the other not. These two hearts were bathed in saline solution and connected to the mechanical device to record heart beats. Then the vagus nerve of one heart (the donor heart) was electrically stimulated. This caused the donor heart slow down, as expected. Loewi took the liquid passing though the donor heart and applied it to the second heart (the recipient heart). Consequently, the recipient heart beat also slower, proving that some soluble chemical released from vagus nerve acted on the recipient heart directly. Loewi named this liquid "Vagusstoff".

Loewi’s experiment: synaptic signaling uses chemical messengersn

Fig.1: Loewi’s most famous experiment which shows that synaptic signaling uses chemical messengers.(Credit: Nrets)

While seven years before Loewi discovered Vagusstoff, Henry Hallett Dale and his colleagues had identified a chemical, acetylcholine, from fungus ergot which stimulated organs in a similar manner. Henry Dale then hypothesized that the Vagusstoff and acetylcholine might mean the same thing. This had been proved when he further found that acetylcholine was produced naturally in mammals from nerve endings in many tissues and organs than heart.

The chemicals known as neurotransmitters, such as acetylcholine, are the major way of transmission of nerve impulses. For their discovery, Otto Loewi and Henry Hallett Dale were awarded Nobel Prize in Physiology or Medicine in 1936. And Otto Loewi’s inspiration from his dream probably suggests that when the mind rests, the subconscious whispers.