LIGAND BINDING

Binding of the transmitter substance is the initial step in the function of synaptic receptors. In this binding process, a precise molecular match is made between the nerve-released transmitter and the receptor binding pocket. When this molecular union is made correctly, small changes occur in the structure of the receptor binding site that are amplified into larger changes that propagate into a global shape change that opens the receptor pore.

Once the pore opens, ions flow through it in the direction of their electrochemical gradients. The receptor binding site is the predominant site targeted by drugs needed to silence or activate receptors for therapeutic reasons. Drugs known as antagonists form a stable union with the receptor binding site, but cannot elicit the conformational changes that open the ionic pore. On the other hand, drugs known as agonists mimic the binding and structural changes elicited by the natural transmitter substance.

ACh binding site occupied by the neuromuscular blocker, Curare.

Once the agonist has bound, the receptor channel opens in an all or nothing fashion. That is why synaptic receptors are often described as "chemically-activated digital switches." The lag between agonist binding and channel opening has been measured and shown to be about 0.0001 of a second. Communication between binding site and pore is allosteric, meaning action at a distance, and requires a precise but yet unknown interplay between these two distinct parts of the receptor structure.

Once the pore opens, it closes in about 0.001 of a second to prepare for the next impulse of agonist. Such rapid opening and closing of synaptic receptors is ideal for voluntary movement, touch and vision, for example. It is vital to understand the process of receptor channel opening because many diseases of synaptic receptors alter this process.