The cytoskeleton modulates gating of the voltage-dependent sodium channel in heart.. Undrovinas, A. I., G. S. Shander, and J. C. Makielski. Henry Ford Heart and Vascular Institute, Division of Cardiovascular Medicine, Detroit, MI 48202-2689, The Department of Medicine, Section of Cardiology, The University of Chicago, Chicago, IL 60637
APStracts 2:0022H, 1995.
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 by cell-attached and inside-out patches from rat and rabbit ventricular cardiac myocytes. Cyto-D (20-40 [mu]M) reduced whole cell peak sodium current by 20% within 12 min and slowed current decay without affecting steady-state voltage-dependent availability or recovery from inactivation. Brief treatments (< 10-15 min ) of cell-attached patches by Cyto-D (20 [mu]M) in the bath induced short bursts of Na channel openings and prolonged decays of ensemble averaged currents. Bursting of the Na channel was more pronounced when the cell suspension was pretreated with Cyto-D (20 [mu]M) for 1 hour prior to seal formation. Application of Cyto-D on the cytoplasmic side of inside-out patches resulted in more dramatic gating changes. Peak open probability was reduced by > 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. 

Received 20 June 1994; accepted in final form 11 January 1995
APS Manuscript Number H545-4.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 24 February 1995.