Synaptic transmission was widely expected to continue electrically across the junction between excitable cells.

Nerve impulses travel along nerve cells as electrical signals, so it once seemed natural to assume that the signal simply continued electrically into the next cell.

The difficult point was the synapse: the tiny junction where a nerve cell communicates with another nerve cell, muscle cell, or gland. Does electricity cross that junction directly, or does the first cell release a chemical signal?

Otto Loewi provided powerful evidence for the chemical route in 1921. He stimulated the vagus nerve of a frog heart, which slowed the heartbeat. He then transferred fluid from around that heart to a second heart, and the second heart slowed too. Something released into the fluid had carried the signal. That substance was later identified as acetylcholine, one of the chemicals now called neurotransmitters.

At a chemical synapse, the first cell releases a neurotransmitter. The molecule crosses the tiny gap and binds to receptors on the next cell, changing its activity.

Chemical transmission turned out to dominate in vertebrate nervous systems, but electrical synapses also exist. At those junctions, channels connect neighboring cells closely enough for electrical current to pass directly between them. The old mistake was treating one mechanism as universal.