Molecular mechanisms of regulation of fast-inactivating voltage-dependent transient outward K+ current in mouse heart by cell volume changes

摘要: The Kv4.2/4.3 channels are the primary subunits that contribute to fast-inactivating, voltage-dependent transient outward K+ current (Ito,fast) in heart. Ito,fast is critical determinant of early repolarization cardiac action potential and plays an important role adaptive remodelling myocytes, which usually causes cell volume changes, during myocardial ischaemia, hypertrophy heart failure. It not known, however, whether regulated by changes. In this study we investigated molecular mechanism for regulation native mouse left ventricular myocytes. Hyposmotic swelling caused a marked increase densities peak significant shortening phase 1 duration. gating properties were, altered changes volume. presence either protein kinase C (PKC) activator (12,13-dibutyrate) or phosphatase inhibitors (calyculin A okadaic acid), hyposmotic failed further up-regulate Ito,fast. When expressed NIH/3T3 cells, both Kv4.2 Kv4.3 were also strongly same voltage-independent but PKC- phosphatase-dependent manner as seen We conclude through phosphorylation/dephosphorylation pathway mediated PKC serine/threonine phosphatase(s). These findings suggest novel electrical structural myocytes response hypertrophy, ischaemia reperfusion.