K currents in ventricular cardiomyocytes of p.N98S-calmodulin mutant mice.

Missense mutations in calmodulin (CaM)-encoding genes are associated with life-threatening ventricular arrhythmia syndromes. Here, we investigated a role of cardiac K channel dysregulation in arrhythmogenic long QT syndrome (LQTS) using a knock-in mouse model heterozygous for a recurrent mutation (p.N98S) in the gene (Calm1).

Identification of nonhistone substrates of the lysine methyltransferase PRDM9.

Lysine methylation is a dynamic, posttranslational mark that regulates the function of histone and nonhistone proteins. Many of the enzymes that mediate lysine methylation, known as lysine methyltransferases (KMTs), were originally identified to modify histone proteins but have also been discovered to methylate nonhistone proteins. In this work, we investigate the substrate selectivity of the KMT PRDM9 to identify both potential histone and nonhistone substrates.

CaMKII Inhibition Attenuates Distinct Gain-of-Function Effects Produced by Mutant Nav1.6 Channels and Reduces Neuronal Excitability.

Aberrant Nav1.6 activity can induce hyperexcitability associated with epilepsy. Gain-of-function mutations in the gene encoding Nav1.

Distinctive Properties and Powerful Neuromodulation of Na1.6 Sodium Channels Regulates Neuronal Excitability.

Voltage-gated sodium channels (Navs) are critical determinants of cellular excitability. These ion channels exist as large heteromultimeric structures and their activity is tightly controlled. In neurons, the isoform Na1.

Neurohormonal Regulation of I in Heart Failure: Implications for Ventricular Arrhythmogenesis and Sudden Cardiac Death.

Heart failure (HF) results in sustained alterations in neurohormonal signaling, including enhanced signaling through the sympathetic nervous system and renin-angiotensin-aldosterone system pathways. While enhanced sympathetic nervous system and renin-angiotensin-aldosterone system activity initially help compensate for the failing myocardium, sustained signaling through these pathways ultimately contributes to HF pathophysiology. HF remains a leading cause of mortality, with arrhythmogenic sudden cardiac death comprising a common mechanism of HF-related death.