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Departments of *Anesthesiology, Neurology and Neurophysiology, and Biometrics, Hannover Medical School, Hannover, Germany; and University Department of Anaesthesia, The University of Liverpool, Liverpool, United Kingdom
Address correspondence and reprint requests to Dr. Gertrud Haeseler, Department of Anesthesiology, OE8050, Hannover Medical School, D-30623 Hannover, Germany. Address e-mail to Haeseler.Gertrud{at}MH-Hannover.de
Propofol decreases muscle tone in the absence of neuromuscular blocking drugs. This effect probably cannot be attributed solely to central nervous depression. We studied the effects of propofol on heterologously expressed skeletal muscle sodium channels. Our hypothesis was that the decrease in muscle tone may partly be attributed to an interaction of propofol with sarcolemmal sodium channels. Cells were voltage clamped and whole-cell sodium inward currents were recorded in the absence and presence of propofol. When depolarizing pulses to 0 mV were started from a holding potential close to the normal resting potential of muscle (-70 mV), or when a 2.5-s prepulse inducing slow inactivation was applied before the test pulse at -100 mV, a significant reduction in the peak current amplitude was achieved by 10 and 5 µM propofol, respectively (P < 0.001). Half-maximum blocking concentrations with these protocols were 23 and 22 µM. Blocking potency increased at depolarized membrane potentials with the fraction of inactivated channels; the estimated dissociation constant Kd from the inactivated state was 4.6 µM. These results suggest that propofol significantly blocks sarcolemmal sodium channels at clinically relevant concentrations while maintaining potentials close to the physiological resting potential.
Implications: Voltage-gated sodium channels mediate the initiation and propagation of action potentials along the sarcolemma. Results from our study show that those channels are targeted and blocked in a concentration- and voltage-dependent manner by propofol. This mechanism may contribute to the reduction in muscle excitability.
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