Sodium channel in the context of Sodium ions

Hyperpolarization is a change in a cell's membrane potential that makes it more negative. Cells typically have a negative resting potential, with neuronal action potentials depolarizing the membrane. When the resting membrane potential is made more negative, it increases the minimum stimulus needed to surpass the needed threshold. Neurons naturally become hyperpolarized at the end of an action potential, which is often referred to as the relative refractory period. Relative refractory periods typically last 2 milliseconds, during which a stronger stimulus is needed to trigger another action potential. Cells can also become hyperpolarized depending on channels and receptors present on the membrane, which can have an inhibitory effect.

Hyperpolarization is often caused by efflux of K (a cation) through K channels, or influx of Cl (an anion) through Cl channels. On the other hand, influx of cations, e.g. Na through Na channels or Ca through Ca channels, inhibits hyperpolarization. If a cell has Na or Ca currents at rest, then inhibition of those currents will also result in hyperpolarization. This voltage-gated ion channel response is how the hyperpolarization state is achieved.

A membrane transport protein is a membrane protein involved in the movement of ions, small molecules, and macromolecules such as another protein, across a biological membrane. Transport proteins are integral transmembrane proteins, that is: they exist permanently within and span the membrane, across which they transport substances. The proteins may assist in the movement of substances by facilitated diffusion, active transport, osmosis, or reverse diffusion. The two main types of proteins involved in such transport are broadly categorized as either channels or carriers (a.k.a. permeases or transporters). Examples of channel/carrier proteins include the GLUT 1 uniporter, sodium channels, and potassium channels. The solute carriers and atypical SLCs are secondary active or facilitative transporters in humans. Collectively membrane transporters and channels are known as the transportome. Transportomes govern cellular influx and efflux of, not only ions and nutrients, but drugs as well.

Anticonvulsants (also known as antiepileptic drugs, antiseizure drugs, or anti-seizure medications (ASM)) are a diverse group of pharmacological agents used in the treatment of epileptic seizures. Anticonvulsants are also used in the treatment of bipolar disorder and borderline personality disorder, since many seem to act as mood stabilizers, and for the treatment of neuropathic pain. Anticonvulsants suppress the uncontrolled and excessive firing of neurons during seizures and in doing so can also prevent the spread of the seizure within the brain.

Conventional antiepileptic drugs have diverse mechanisms of action but many block sodium channels or enhance γ-aminobutyric acid (GABA) function. Several antiepileptic drugs have multiple or uncertain mechanisms of action. Next to voltage-gated sodium channels and components of the GABA system, their targets include GABA_A receptors, the GABA transporter type 1, and GABA transaminase. Additional targets include voltage-gated calcium channels, SV2A, and α2δ. By blocking sodium or calcium channels, antiepileptic drugs reduce the release of the excitatory neurotransmitter glutamate, whose release is considered to be elevated in epilepsy, but also that of GABA. This is probably a side effect or even the actual mechanism of action for some antiepileptic drugs, since GABA can itself, directly or indirectly, act pro-convulsively. Another potential target of antiepileptic drugs is the peroxisome proliferator-activated receptor alpha.

Gap junctions are membrane channels between adjacent cells that allow the direct exchange of cytoplasmic substances, such as small molecules, substrates, and metabolites. Gap junctions were first described as close appositions alongside tight junctions, but later electron microscopy studies saw them renamed as gap junctions to distinguished them from tight junctions. They bridge a 2-4 nm gap between cell membranes.

Gap junctions use protein complexes known as connexons, composed of connexin proteins to connect one cell to another. Gap junction proteins include the more than 26 types of connexin, as well as at least 12 non-connexin components that make up the gap junction complex or nexus, including the tight junction protein ZO-1—a protein that holds membrane content together and adds structural clarity to a cell, sodium channels, and aquaporin.

The epithelial sodium channel (ENaC), (also known as amiloride-sensitive sodium channel) is a membrane-bound ion channel that is selectively permeable to sodium ions (Na). It is assembled as a heterotrimer composed of three homologous subunits α or δ, β, and γ, These subunits are encoded by four genes: SCNN1A, SCNN1B, SCNN1G, and SCNN1D. The ENaC is involved primarily in the reabsorption of sodium ions at the collecting ducts of the kidney's nephrons. In addition to being implicated in diseases where fluid balance across epithelial membranes is perturbed, including pulmonary edema, cystic fibrosis, COPD and COVID-19, proteolyzed forms of ENaC function as the human salt taste receptor.

The apical membranes of many tight epithelia contain sodium channels that are characterized primarily by their high affinity for the diuretic blocker amiloride. These channels mediate the first step of active sodium reabsorption essential for the maintenance of body salt and water homeostasis. In vertebrates, the channels control reabsorption of sodium in kidney, colon, lung and sweat glands; they also play a role in taste perception.