ALTERED SODIUM CURRENT RESPONSE TO INTRACELLULAR FATTY-ACIDS IN HALOTHANE-HYPERSENSITIVE SKELETAL-MUSCLE

Biopsies of human skeletal muscle were analyzed by an in vitro contrac ture test (IVCT) for responsiveness to a halothane challenge: noncontr acting (nonresponsive; IVCT-) and contracting (IVCT+). A muscle biopsy that is IVCT+ indicates potential malignant hyperthermia (MH) suscept ibility. Primary cultures were grown from portions of the skeletal mus cle biopsies, and voltage-activated currents were measured by whole ce ll recording in the presence or absence of 2-5 mu M intracellular arac hidonic or oleic acids. In untreated IVCT- cells, Na+ currents were pr edominantly tetrodotoxin (TTX) insensitive, indicating that most of th e current was carried through the embryonic SkM2 isoform of the Na+ ch annel. Inclusion of fatty acids in the recording pipette of IVCT- cell s produced an increase in voltage-activated Na+ currents during 20 min of recording. Approximately 70% of currents in fatty acid-treated cel ls 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 absenc e of added fatty acid, thus showing a relatively large baseline functi onal expression of SkM1 channels. Addition of fatty acids to the recor ding pipette produced little further change in the magnitude or TTX se nsitivity of the whole cell currents in IVCT+ cells, suggesting altere d functional regulation of Na+ channels in MH muscle.