Altered sodium current response to intracellular fatty acids in
halothane-hypersensitive skeletal muscle.
Wieland, Steven J., Qi-Hua Gong, Jeffrey E. Fletcher, and Henry
Department of Anatomy and Neurobiology and Department of
Anesthesiology, Medical College of Pennsylvania and Hahnemann
University, Broad and Vine, Philadelphia, PA 19102
APStracts 3:0035C, 1996.
Biopsies of human skeletal muscle were analyzed by an in vitro
contracture test (IVCT) for responsiveness to a halothane challenge:
non-contracting (non-responsive), IVCT(-), and contracting, IVCT(+).
A muscle biopsy which 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 to 5 M intracellular arachidonic or oleic acids. In
untreated IVCT(-) cells, sodium currents were predominantly TTX
insensitive, indicating that most of the current was carried through
the embryonic SkM2 isoform of the sodium channel. Inclusion of fatty
acids in the recording pipette of IVCT(-) cells produced an increase
in voltage-activated sodium currents during 20 minutes of recording.
Approximately 70% of currents in fatty-acid treated cells were
tetrodotoxin (TTX) sensitive, indicating activation of the adult SkM1
isoform of the sodium channel. In contrast to IVCT(-) cells, IVCT(+)
cells expressed sodium currents which 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 sodium channels in MH muscle.
Received 15 May 1995; accepted in final form 10 January 1996.
APS Manuscript Number C269-5.
Article publication pending Am. J. Physiol. (Cell Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 29 January 96