INa is responsible for the fast upstroke of the action potential, and as such plays a crucial role in impulse propagation through the heart.

Upon a stimulus (through conduction by a neighboring cell), the membrane depolarizes and NaV1.5 channels open through the outward movement of the S4 segments, leading to the initiation of the action potential.

[12] Trafficking, function and structure of NaV1.5 can be affected by the many protein interaction partners that have been identified to date (for an extensive review, see Abriel et al.

In general, beta-subunits increase function of NaV1.5, either by change in intrinsic properties or by affecting the process of trafficking to the cell surface.

Also, mutations may act as a disease modifier, especially in families where lack of direct causality is reflected by complex inheritance patterns.

SCN5A mutations are believed to be found in a disproportionate number of people who have Irritable Bowel Syndrome, particularly the constipation-predominant variant (IBS-C).

[7][29] The resulting defect leads to disruption in bowel function, by affecting the Nav1.5 channel, in smooth muscle of the colon and pacemaker cells.

[7] Researchers managed to treat a case of IBS-C with mexiletine to restore Nav1.5 channels, reversing constipation and abdominal pain.

[30][unreliable medical source][31] Genetic variations in SCN5A, i.e. single nucleotide polymorphisms (SNPs) have been described in both coding and non-coding regions of the gene.

In the cardiovascular field this powerful technique has been used to detect loci involved in variation in electrocardiographic parameters (i.e. PR-, QRS- and QTc-interval duration) in the general population.

[16] The rationale behind this technique is that common genetic variation present in the general population can influence cardiac conduction in non-diseased individuals.