Cardiac Expression Of Fetal And Adult Scn5a Isoforms In Sudden Unexplained Infant Death (Suid)

Sodium Voltage-Gated Channel Alpha Subunit 5 (SNC5A) plays a vital role in cardiac depolarization and has been implicated in Long QT Syndrome and sudden cardiac death. SCN5A encodes fetal and adult isoforms, differing by splicing of exon 6A or 6B, respectively. Fetal SCN5A decreases peak sodium current, leading to slower channel activation and inactivation and providing a potential substrate for arrhythmia. Little is known about developmental expression of these isoforms. We investigated developmental expression of SCN5A isoforms in infants, toddlers, and adults, including expression ratios in SUID cases and controls (0-12 months). We extracted RNA from heart tissue collected at autopsy (fetus-24 months) with 80 SUID cases and 27 controls, and 5 adult donor hearts. RNA Integrity Numbers ranged from 4.8-9.5. Relative SCN5A isoform expression was quantified by qRT-PCR. Non-parametric t-test and ANOVA were used; P<0.05 was considered statistically significant. Our results show a significant stepwise increase in adult/fetal isoform expression with age. Relative expression of adult/fetal SCN5A increased significantly from fetal-4 months to 5-24 months (P<0.0001), and again in adulthood (P<0.0001). There was no significant difference between case and control groups at 0-4 or 0-12 months. Expression of adult/fetal SCN5A increases significantly from birth to 24 months of age and into adulthood. Relative adult/fetal SCN5A expression is lowest during the neonatal period through 4 months, corresponding with the peak incidence of SUID. Further investigation of protein expression of SCN5A isoforms may shed light onto the age-dependent incidence of sudden death.