Intracellular calcium attenuates late current conducted by mutant human cardiac sodium channels.

Background: Mutations of the cardiac voltage-gated sodium channel (SCN5A gene encoding voltage-gated sodium channel [NaV1.5]) cause congenital long-QT syndrome type 3 (LQT3). Most NaV1.

Long QT syndrome-associated mutations in intrauterine fetal death.

Importance: Intrauterine fetal death or stillbirth occurs in approximately 1 out of every 160 pregnancies and accounts for 50% of all perinatal deaths. Postmortem evaluation fails to elucidate an underlying cause in many cases. Long QT syndrome (LQTS) may contribute to this problem.

Calmodulin mutations associated with recurrent cardiac arrest in infants.

Background: Life-threatening disorders of heart rhythm may arise during infancy and can result in the sudden and tragic death of a child. We performed exome sequencing on 2 unrelated infants presenting with recurrent cardiac arrest to discover a genetic cause.

Methods And Results: We ascertained 2 unrelated infants (probands) with recurrent cardiac arrest and dramatically prolonged QTc interval who were both born to healthy parents.

Mechanism of sodium channel NaV1.9 potentiation by G-protein signaling.

Tetrodotoxin (TTX)-resistant voltage-gated Na (Na(V)) channels have been implicated in nociception. In particular, Na(V)1.9 contributes to expression of persistent Na current in small diameter, nociceptive sensory neurons in dorsal root ganglia and is required for inflammatory pain sensation.

Activation of protein kinase C alters the intracellular distribution and mobility of cardiac Na+ channels.

Na(+) current derived from expression of the cardiac isoform SCN5A is reduced by receptor-mediated or direct activation of protein kinase C (PKC). Previous work has suggested a possible role for loss of Na(+) channels at the plasma membrane in this effect, but the results are controversial. In this study, we tested the hypothesis that PKC activation acutely modulates the intracellular distribution of SCN5A channels and that this effect can be visualized in living cells.

Developmentally regulated SCN5A splice variant potentiates dysfunction of a novel mutation associated with severe fetal arrhythmia.

Background: Congenital long-QT syndrome (LQTS) may present during fetal development and can be life-threatening. The molecular mechanism for the unusual early onset of LQTS during fetal development is unknown.

Objective: We sought to elucidate the molecular basis for severe fetal LQTS presenting at 19 weeks' gestation, the earliest known presentation of this disease.