Role of gelsolin in the actin filament regulation of cardiac L-type calcium channels

The actin cytoskeleton is an important contributor to the modulation of the cell function. However, little is known about the regulatory role of this supermolecular structure in the membrane events that take place in the hear t. In this report, the regulation of cardiac myocyte function by actin fila ment organization was investigated in neonatal mouse cardiac myocytes (NMCM ) from both wild-type mice and mice genetically devoid of the actin filamen t severing protein gelsolin (Gsn-/-). Cardiac L-type calcium channel curren ts (I-Ca) were assessed using the whole cell voltage-clamp technique. Addit ion of the actin filament stabilizer phalloidin to wild-type NMCM increased I-Ca by 227% over control conditions. The basal I-Ca of Gsn-/- NMCM was 30 0% higher than wild-type controls. This increase was completely reversed by intracellular perfusion of the Gsn-/- NMCM with exogenous gelsolin. Furthe r, cytoskeletal disruption of either Gsn-/- or phalloidin-dialyzed wild-typ e NMCM with cytochalasin D (CD) decreased the enhanced I-Ca by 84% and 87%, respectively. The data indicate that actin filament stabilization by eithe r a lack of gelsolin or intracellular dialysis with phalloidin increase I-C a, whereas actin filament disruption with CD or dialysis of Gsn-/- NMCM wit h gelsolin decrease Ic,. We conclude that cardiac L-type calcium channel re gulation is tightly controlled by actin filament organization. Actin filame nt rearrangement mediated by gelsolin may contribute to calcium channel ina ctivation.