Loewi's famous experiment, published in 1921, largely answered this question. He dissected out of frogs two beating hearts: one with the vagus nerve which controls heart rate attached, the other heart on its own. Both hearts were bathed in a saline solution (i.e. Ringer's solution). By electrically stimulating the vagus nerve, Loewi made the first heart beat slower. Then, Loewi took some of the liquid bathing the first heart and applied it to the second heart. The application of the liquid made the second heart also beat slower, proving that some soluble chemical released by the vagus nerve was controlling the heart rate. He called the unknown chemical Vagusstoff, naming it after the nerve and the German word for substance. It was later found that this chemical corresponded to acetylcholine. His experiment was iconic because it was the first to demonstrate the endogenous release of a chemical substance that could cause a response in the absence of electrical stimulation. It paved the way for the understanding that the electrical signaling event (action potential) causes a chemical event (release of neurotransmitter from synapses) that is ultimately the effector on the tissue.