Nicotinic Acetylcholine Receptors in Health and Disease
Ronald J. Lukas, PhD, Director
Chemical signaling between nerve cells and their targets occurs in anatomically specialized areas called synapses. When an electrical impulse reaches the terminus of a nerve cell axon, balloon-like synaptic vesicles inside the cell filled with chemical neurotransmitters fuse with the plasma membrane at the axon terminal. This fusion at one point creates an omega structure. As synaptic vesicles explode into the extracellular space, they release neurotransmitters. These chemical messengers then cross the narrow synaptic cleft.
Some neurotransmitters dock at binding sites on a structurally matched neurotransmitter receptor. These receptors are located in the plasma membrane of the target cell. This membrane consists of 2-sided bed of phospholipids with polar heads facing the inside or outside of the cell, linked in the middle of the membrane by interactions between their hydrophobic tails. At rest, the channel at the center of each receptor is closed. The plasma membrane is impermeable to sodium (Na+), potassium (K+), or calcium ions (Ca2+), and the target cell is electrically silent. However, when enough neurotransmitters dock at binding sites, the shape of the neurotransmitter receptor changes, causing the channel to widen and allowing ions to flow through the channel. If enough sodium ions flow inward, electrical activity in the target cell is triggered. If there is adequate electrical activity, an electrical impulse is propagated in the target cells, and the entire process repeats itself. Outward flow of positively charged potassium ions flowing through specialized channels neutralizes electrical activity in the cell, returning it to the resting state. The inward flow of calcium ions can have many effects on signaling within the cell.
Acetylcholine is the natural chemical neurotransmitter made by many nerve cells. Nicotine from tobacco has many of the same effects as acetylcholine. Both acetylcholine and nicotine exert their effects on the nervous system by acting on nicotinic acetylcholine receptors, which are sodium (and calcium) ion-permeable neurotransmitter receptors that function as acetylcholine- or nicotine-gated ion channels.