Cytochalasin D (20-40 microM) reduced whole cell peak Na+ current by 20% and peak open probability by >50%, suggesting the cytoskeleton regulates cardiac Na+ channel gating.
Disruption of actin polymerization with cytochalasin D alters cardiac Na+ channel gating, indicating the cytoskeleton regulates specific functions of integral membrane proteins.
To investigate the role of the cytoskeleton in cardiac Na+ channel gating, the action of cytochalasin D (Cyto-D), an agent that interferes with actin polymerization, was studied by whole cell voltage clamp and cell-attached and inside-out patches from rat and rabbit ventricular cardiac myocytes. Cyto-D (20-40 microM) reduced whole cell peak Na+ current by 20% within 12 min and slowed current decay without affecting steady-state voltage-dependent availability or recovery from inactivation. Brief treatments ( 50% within 20 min, and long bursts of openings occurred. Washout of Cyto-D did not restore ensemble-averaged current amplitude, but burst duration decreased toward control values. Cyto-D also induced an additional slower component to open and closed times. These results suggest that Cyto-D, through effects on cytoskeleton, induced cardiac Na+ channels to enter a mode characterized by a lower peak open probability but a greater persistent activity as if the inactivation rate was slowed. The cytoskeleton, in addition to localizing integral membrane proteins, apparently also plays a role in regulating specific detailed functions of integral membrane proteins such as the gating of Na+ channels.
Undrovinas et al. (1995) studied this question. Cytochalasin D vs. Control/baseline was evaluated on Whole cell peak Na+ current and gating changes. Cytochalasin D (20-40 microM) reduced whole cell peak Na+ current by 20% and peak open probability by >50%, suggesting the cytoskeleton regulates cardiac Na+ channel gating.