The Sialyltransferase, ST3Gal-IV, Modulates Cardiac Action Potential Waveforms And IK

Abstract

Atrial arrhythmias can be caused by changes in atrial action potential (AP) waveform or conduction. The regulated activity of ion channels, including voltage-gated potassium (Kv) channel isoforms, is crucial to normal AP waveform. Each Kv channel isoform is uniquely glycosylated; glycans are typically terminated by sialic acid residues. Reports have shown sialic acids can modulate Kv channel gating through isoform-specific mechanisms. Here, we questioned whether regulated sialylation alters AP waveforms and voltage-gated K+ currents (IK) produced in the atrium. AP waveform parameters and two types of IK, the transient outward, Ito, and the slowly inactivating, IK,slow, were compared in atrial myocytes isolated from neonatal control versus ST3Gal-IV knockout animals. ST3Gal-IV is a sialyltransferase expressed at uniform levels throughout the heart and adds sialic acid residues to N- and O-linked glycans through α2-3 linkages. ECG recordings suggest that cardiac conduction/rhythm are altered in ST3Gal-IV(-/-) animals. AP duration (APD) was prolonged significantly in ST3Gal-IV(-/-) atrial myocytes compared to control APD. APD10, APD50, and APD90 values for ST3Gal-IV(-/-) myocytes were ∼50-80% greater than control values (p 10 mV to more depolarized potentials in ST3Gal-IV(-/-) myocytes compared to control (p < 0.001); a depolarizing shift in activation voltage will lead to fewer Kv channels active at a membrane potential, effectively reducing Kv channel activity. These data suggest that the regulated expression of a single sialyltransferase, ST3Gal-IV, can alter IK, thus modulating the rate of atrial repolarization and potentially leading to arrhythmias.