AJP - Heart and Circulatory Physiology, Vol 260, Issue 3 759-H769, Copyright © 1991 by American Physiological Society
Effects of charged amphiphiles on cardiac cell contractility are mediated via effects on Ca2+ current
J. A. Post, S. Ji, K. S. Leonards and G. A. Langer
Department of Medicine and Physiology, University of California, School of Medicine, Los Angeles 90024-1760.
Exposure of isolated adult rabbit myocytes to the negatively charged
amphiphile dodecylsulfate (DDS; 10 microM) increased the contraction
amplitude to 185% of control. The positively charged amphiphile
dodecyltrimethylammonium (DDTMA; 10 microM) decreased the amplitude to 58%.
DDS increased Ca2+ uptake by the same cells, but this uptake was partially
prevented by nifedipine. DDTMA had no effect on Ca2+ uptake. Ca2+ binding
to isolated sarcolemma of neonatal heart cells was increased by 10 microM
DDS and, at higher concentrations, reduced by DDTMA. Single-cell
voltage-clamp studies, using isolated rabbit myocytes, showed that DDS
enhanced L-type Ca2+ currents (ICa,L), whereas DDTMA depressed ICa,L. DDS
shifted current-voltage (I-V) and isochronal inactivation curves of ICa,L
in the negative direction, whereas DDTMA shifted them in positive
direction. Furthermore, DDS depressed T-type Ca2+ currents (ICa,T), and
DDTMA enhanced ICa,T. The inotropic effects of the amphiphiles are
therefore mediated to a significant degree by ICa,L. The shifts in the I-V
and inactivation curves of ICa,L and the effect on ICa,T can be explained
by changes in the actual membrane potential (Em), induced by the insertion
of the amphiphiles in the outer monolayer of the sarcolemma. However, the
changes in the Em do not explain the effect on the maximal current,
indicating effects on the channel per se, possibly by an alteration of the
lipid environment.
