A gap narrower than a virus proved that brain cells talk chemically
Into the twentieth century, most scientists pictured nerve cells passing signals electrically, like wires spliced together. Then Santiago Ramón y Cajal spotted a gap of just 20 to 40 nanometres between neurons. Something had to cross it, and in 1921 Otto Loewi showed, using frog hearts, that the messenger was a chemical.
Loewi's frog experiments demonstrated that heart rate could be slowed by chemical signals from the vagus nerve, and he is credited with identifying acetylcholine, the first neurotransmitter known. Researchers have since catalogued more than a hundred, though nobody knows the full count in humans. Familiar names include glutamate, GABA, glycine, dopamine and noradrenaline. Many are built cheaply from amino acids in a handful of steps; serotonin, for instance, starts life as tryptophan. Others are bulky peptides, purines such as ATP, or even gases like nitric oxide and carbon monoxide, which are made on demand rather than stockpiled.
Most transmitters wait in tiny sacs called vesicles near the tip of the sending cell. When an electrical impulse arrives, calcium floods in through channels that open in response to voltage, and the vesicles fuse with the membrane and spill their contents into the cleft. What happens next depends entirely on the receptor on the far side. The same molecule can excite one cell, calm another, or subtly retune a third, for example by changing how many receptors it displays. A receiving neuron fires only if the excitatory nudges outweigh the inhibitory ones.
Anatomy helps. Excitatory synapses usually sit on the branching dendrites and carry round vesicles, while inhibitory ones cluster on the cell body, near the point where impulses begin, and have flattened vesicles. Blocking a signal there is efficient, like closing a starting gate before a racehorse can bolt.
Clearing the cleft matters as much as filling it, or receptors would stay switched on. Transmitters can drift away to be mopped up by star-shaped glial cells called astrocytes, be chopped apart by enzymes, or be pumped back into the sending cell for reuse. Acetylcholine is split by acetylcholinesterase, and its choline is recycled. Cocaine works by jamming the pump that retrieves dopamine, so the signal lingers and keeps stimulating its targets.
Source: Neurotransmitter
