Halothane-induced malignant hyperthermia: Creatine phosphate concentration in skeletal muscle as an early indicator of the onset of the syndrome

beta-Adrenergic stimulation has been reported to inhibit insulin-stimulated glucose transport in adipocytes. This effect has been attributed to a decrease in the intrinsic activity of the GLUT-4 isoform of the glucose transporter that is mediated by phosphorylation of GLUT-4. Early studies showed no inhibition of insulin-stimulated glucose transport by epinephrine in skeletal muscle. The purpose of this study was to determine the effect of epinephrine on GLUT-4 phosphorylation, and reevaluate the effect of beta-adrenergic stimulation on insulin-activated glucose transport, in skeletal muscle. We found that 1 microM epinephrine, which raised adenosine 3',5'-cyclic monophosphate approximately ninefold, resulted in GLUT-4 phosphorylation in rat skeletal muscle but had no inhibitory effect on insulin-stimulated 3-O-methyl-D-glucose (3-MG) transport. In contrast to 3-MG transport, the uptakes of 2-deoxyglucose and glucose were markedly inhibited by epinephrine treatment. This inhibitory effect was presumably mediated by stimulation of glycogenolysis, which resulted in an increase in glucose 6-phosphate concentration to levels known to severely inhibit hexokinase. We conclude that 1) beta-adrenergic stimulation decreases glucose uptake by raising glucose 6-phosphate concentration, thus inhibiting hexokinase, but does not inhibit insulin-stimulated glucose transport and 2) phosphorylation of GLUT-4 has no effect on glucose transport in skeletal muscle.

Download Full-text

Chapter 23 Skeletal muscle channelopathies: myotonias, periodic paralyses and malignant hyperthermia

Handbook of Clinical Neurophysiology ◽

10.1016/s1567-4231(09)70133-9 ◽

2003 ◽

pp. 457-483 ◽

Cited By ~ 1

Author(s):

Frank Lehmann-Horn ◽

Holger Lerche ◽

Karin Jurkat-Rott

Keyword(s):

Skeletal Muscle ◽

Malignant Hyperthermia ◽

Periodic Paralyses ◽

Skeletal Muscle Channelopathies

Download Full-text

Role of leukocytes in reperfusion injury of skeletal muscle after partial ischemia

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1989.257.4.h1068 ◽

1989 ◽

Vol 257 (4) ◽

pp. H1068-H1075 ◽

Cited By ~ 4

Author(s):

J. Yokota ◽

J. P. Minei ◽

G. A. Fantini ◽

G. T. Shires

Keyword(s):

Skeletal Muscle ◽

Reperfusion Injury ◽

White Blood Cells ◽

Creatine Phosphate ◽

High Energy ◽

Control Group ◽

Base Line ◽

Infrarenal Aorta ◽

Sprague Dawley ◽

Membrane Injury

These experiments evaluated the leukocyte as a potential source of oxygen free radical (OFR) generation during reperfusion injury in post-ischemic skeletal muscle. The infrarenal aorta of heparinized Sprague-Dawley rats was clamped for 90 min, declamped, and reperfused for 60 min. Hindlimb muscle resting transmembrane potential difference (Em) and high-energy phosphate content were determined at base line, during ischemia, and on reperfusion. Four groups were studied: a control group, a second group receiving superoxide dismutase and catalase (SOD + CAT) on declamping, a third group receiving dimethylmyleran (DMM) 7 days before the experiment to obtain a selective leukopenia (white blood cells = 1,210 +/- 144/mm3, neutrophils = 1.2%), and a fourth group pretreated with allopurinol (ALLO). During the ischemic period, resting Em was significantly depolarized (-78.6 +/- 0.5 mV from -90.3 +/- 0.3; P less than 0.05) in the control group, whereas creatine phosphate (CP) was depleted and ATP maintained. Data collected during the ischemic phase of the three other groups were similar to the control group (P = NS). On reperfusion, persistent depolarization of resting Em was observed despite restoration of muscle CP content in the control and ALLO groups (-75.4 and -77.0 mV, respectively). In contrast, significant repolarization of resting Em was noted after reperfusion in the SOD + CAT and DMM groups (-86.5 and -88.6 mV, respectively). These data implicate leukocyte-generated OFR as mediators of reperfusion-associated cellular membrane injury in postischemic skeletal muscle.

Download Full-text