Sphingolipid actions on sodium and calcium currents of rat
ventricular myocytes.
Yasui, Kenji, and Philip Palade.
Departments of Physiology & Biophysics and of Pharmacology &
Toxicology, University of Texas Medical Branch, Galveston, TX 77555
-0641, USA
APStracts 2:0321C, 1995.
Sphingosine, an endogenous phospholipid known to produce significant
decreases in myoplasmic calcium transients, was shown to have a
pronounced inhibitory effect on inward sodium and L-type calcium
currents in rat ventricular myocytes. Sphingosine action was
accompanied by a slowing of inactivation of both kinds of current.
Sphingosine and sphingosylphosphorylcholine (SPC) both caused
depolarizing shifts in the activation curves for the two channels. In
tests on calcium currents, sphingosine showed no high affinity for
inactivated states nor exhibited any use dependence. The mechanism of
the blocking action of sphingosine does not appear to involve effects
on bulk surface charge nor, at least for calcium channels, a voltage
-dependent block. Instead the results appear most consistent with an
effect of sphingosine on channel gating. The shift in the voltage
dependence of channel activation by sphingosine and SPC appears
likely to be a feature of both the hydrocarbon chains and the net
positive charge of these amphiphiles.
Received 3 April 1995; accepted in final form 28 August 1995.
APS Manuscript Number C190-5.
Article publication pending Am. J. Physiol. (Cell Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 23 September 1995.