What is the 4-AP model of epilepsy?

Answer: 4-AP mimics epilepsy by inducing seizures. 4-AP blocks potassium channels.

epilepsy 4-ap

Epilepsy is a potentially life threatening neurological disorder. It is the fourth most common neurological disorder, and about 1 in 26 Americans will develop some sort of epileptic activity in their lifetimes. A single seizure is not usually indicative of an epilepsy diagnosis; generally two unprovoked seizures in conjunction with brain scans needs to be observed before a diagnosis is to be made.

It’s primary symptom is the appearance of seizures of varying intensity. These are rarely the same between patients. Seizures can cause convulsions and a loss of control of limbs. But not all seizures manifest themselves equally - other signs of seizures include loss of consciousness or temporary confusion.

To search for a cure for epilepsy, researchers use animal models for the disease. Usually, diseases are modeled in rodents such as rats and mice. Therapeutic drugs are then tested in the laboratory setting to determine if the compound is able to decrease the severity of the disease.

However, rodents do not spontaneously have seizures. A chemical must be introduced that induces seizure like activity. The pharmacological agent in question can then be given to the animal to see if the seizure severity or duration is changed.

4-AP is compound that induces seizures in mice (Effects of anticonvulsant drugs on 4-aminopyridine-induced seizures in mice). It is an inhibitor of potassium channels. 4-AP therefore increases the excitability of cells through its action on these K channels. This increase in neuronal network activity produces symptoms of epilepsy in animal models of the disease.

Normally, some potassium channels function as passive flow channels. Potassium often moves along its concentration gradient to maintain a cell membrane close to the reversal potential for K, which is usually negative. By having potassium channels open, the cell is prevented from depolarizing. By blocking these K channels, 4-AP causes an increase in membrane excitability.

Currently, there are therapeutics available to decrease the symptoms of epilepsy, including diazepam, gabapentin, topiramate, or valproate. Surgery has also been effective at decreasing seizures, but because this carries tremendous risks, this procedure is reserved for patients with severe cases that are not reflexive to drug therapy. These surgical treatments often involve the severing of the corpus callosum, the major white matter tract that connects both hemispheres of the brain.

There is some indication that family history may contribute to epilepsy, but for the most part, it's origin is unknown. It can be triggered by extremely low blood sugar, head injuries, or by certain visual stimuli. Additionally, seizures are one symptom of severe alcohol withdrawal.