AJP - Cell Physiology, Vol 271, Issue 1 C347-C353, Copyright © 1996 by American Physiological Society
Altered sodium current response to intracellular fatty acids in halothane-hypersensitive skeletal muscle
S. J. Wieland, Q. H. Gong, J. E. Fletcher and H. Rosenberg
Department of Anatomy, Medical College of Pennsylvania, Philadelphia 19102, USA.
Biopsies of human skeletal muscle were analyzed by an in vitro contracture
test (IVCT) for responsiveness to a halothane challenge: noncontracting
(nonresponsive; IVCT-) and contracting (IVCT+). A muscle biopsy that is
IVCT+ indicates potential malignant hyperthermia (MH) susceptibility.
Primary cultures were grown from portions of the skeletal muscle biopsies,
and voltage-activated currents were measured by whole cell recording in the
presence or absence of 2-5 microM intracellular arachidonic or oleic acids.
In untreated IVCT- cells, Na+ currents were predominantly tetrodotoxin
(TTX) insensitive, indicating that most of the current was carried through
the embryonic SkM2 isoform of the Na+ channel. Inclusion of fatty acids in
the recording pipette of IVCT- cells produced an increase in
voltage-activated Na+ currents during 20 min of recording. Approximately
70% of currents in fatty acid-treated cells were TTX sensitive, indicating
activation of the adult SkM1 isoform of the Na+ channel. In contrast to
IVCT- cells, IVCT+ cells expressed Na+ currents that were predominantly TTX
sensitive even in the absence of added fatty acid, thus showing a
relatively large baseline functional expression of SkM1 channels. Addition
of fatty acids to the recording pipette produced little further change in
the magnitude or TTX sensitivity of the whole cell currents in IVCT+ cells,
suggesting altered functional regulation of Na+ channels in MH muscle.
