Answer: Inactivation refers to a molecular mechanism that blocks a channel.
Ionotropic receptors are transmembrane proteins that allow the conductance of ions through the cell membrane. When an agonist binds to its appropriate receptor, a conformational shift in the structure of the protein allows ions to pass into or out of the cell, based on the concentration gradient. During this state, the ion channel is considered to be activated. As long as the ion channel is activated, ions will continue to enter or exit the cell.
Inactivation refers to a mechanism that is built into the receptor itself. A good example of receptor inactivation has been demonstrated with voltage-gated sodium channels. When the cell membrane reaches a depolarized potential, these channels open. At highly depolarized potentials above 0 mV, an intracellular protein “plug” enters into the ion channel. This plug is tethered to the intracellular side of the protein, and prevents any further ion flux. After the cell returns to the resting potential, the inactivation mechanism reverses itself, and the channel is ready to be activated again by the presence of agonist.
This model of inactivation is called a “ball and chain” model because of the structure of the protein. The part that blocks the pore is the ball. The ball portion is kept close to the intracellular side of the pore by the chain. When the protein is cleaved at the chain, the ball is no longer able to stay close to the pore. As a result, the gate is unable to inactivate, and will remain open as long as a ligand is bound to the extracellular component of the receptor.