KCNQ channels are involved in the regulatory volume decrease response in primary neonatal rat cardiomyocytes

Cardiomyocytes may experience significant cell swelling during ischemia and reperfusion. Such changes in cardiomyocyte volume have been shown to affect the electrical properties of the heart, possibly leading to cardiac arrhythmia. In the present study the regulatory volume decrease (RVD) response of neonatal rat cardiomyocytes was studied in intact single cells attached to coverslips, i.e. with an intact cytoskeleton. The potential contribution of KCNQ (Kv7) channels to the RVD response and the possible involvement of the F-actin cytoskeleton were investigated. The rate of RVD was significantly inhibited in the presence of the KCNQ channel blocker XE-991 (10 and 100 μM). Electrophysiological experiments confirmed the presence of an XE-991 sensitive current and Western blotting analysis revealed that KCNQ1 channel protein was present in the neonatal rat cardiomyocytes. Hypoosmotic cell swelling changes the structure of the F-actin cytoskeleton, leading to a more rounded cell shape, less pronounced F-actin stress fibers and patches of actin. In the presence of cytochalasin D (1 μM), a potent inhibitor of actin polymerization, the RVD response was strongly reduced, confirming a possible role for an intact F-actin cytoskeleton in linking cell swelling to activation of ion transport in neonatal rat cardiomyocytes.