Stimulation of protein kinase C inhibits bursting in disease-linked mutant human cardiac sodium channels

Mutations in SCN5A, the gene coding for the human cardiac Na+ channel alpha-subunit, are associated with variant 3 of the long-QT syndrome (LQT-3). Several LQT-3 mutations promote a mode of Na+ channel gating in which a fraction of channels fail to inactivate, contributing sustained Na+ channel current (Isus), which can delay repolarization and prolong the QT interval. Here, we investigate the possibility that stimulation of protein kinase C (PKC) may modulate Isus, which is prominent in disease-related Na+ channel mutations.