How do sodium channels cause seizures?

Voltage-gated sodium channels initiate action potentials in brain neurons, and sodium channel blockers are used in therapy of epilepsy. Mutations in sodium channels are responsible for genetic epilepsy syndromes with a wide range of severity.

How does epilepsy affect sodium channels?

There are several known causes for epilepsy; one of them is the malfunction of ion channels, resulting from mutations. Voltage-gated sodium channels (NaV) play an essential role in the generation and propagation of action potential, and malfunction caused by mutations can induce irregular neuronal activity.

How does the sodium channel selectivity?

Sodium ion channels selectively transport Na+ cations across the cell membrane. These integral parts of the cell machinery are implicated in regulating the cardiac, skeletal and smooth muscle contraction, nerve impulses, salt and water homeostasis, as well as pain and taste perception.

How do sodium channel blockers work for epilepsy?

Sodium channel blockade is the most common and best-characterized mechanism of currently available antiepileptic drugs (AEDs). AEDs that target sodium channels prevent the return of the channels to the active state by stabilizing the inactive form. In doing so, repetitive firing of the axons is prevented.

How does this lead to seizure activity in the brain?

Nerve cells (neurons) in the brain create, send and receive electrical impulses, which allow the brain’s nerve cells to communicate. Anything that disrupts these communication pathways can lead to a seizure. Some types of seizure disorders may be caused by genetic mutations.

How does epilepsy affect action potential?

During a seizure, the epileptic neurons undergo a prolonged depolarization with continuous bursts of action potentials without an intervening repolarization. The behavioral correlate of this prolonged depolarization is the tonic phase of the seizure.

How does a selectivity filter work?

1 the selectivity filter forms the most constricted part of the conduction pathway. It is so constricted that in order for the K+ ion to pass through most of the waters forming the hydration shell of the ion have to be removed.

What happens if Na channels are blocked?

Complete block of sodium channels would be lethal. However, these drugs selectively block sodium channels in depolarized and/or rapidly firing cells, such as axons carrying high-intensity pain information and rapidly firing nerve and cardiac muscle cells that drive epileptic seizures or cardiac arrhythmias.

What happens when Na channels are blocked?

How do sodium channel blockers work?

A class of drugs that act by inhibition of sodium influx through cell membranes. Blockade of sodium channels slows the rate and amplitude of initial rapid depolarization, reduces cell excitability, and reduces conduction velocity. An anti-anginal drug used for the treatment of chronic angina.