Halothane Increases Membrane Fluidity and Stimulates Sphingomyelin Degradation by Membrane‐Bound Neutral Sphingomyelinase of Synaptosomal Plasma Membranes from Calf Brain Already at Clinical Concentrations

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Abstract
High concentrations of halothane stimulate the degradation of sphingomyelin by neutral sphingomyelinase bound to synaptosomal plasma membranes (SYM) from calf brain up to 50‐fold, and increase membrane fluidity dramatically as measured by fluorescence depolarisation of incorporated 1,6‐diphenylhexatriene (DPH). To investigate the effects of low concentrations of halothane clinical conditions of anaesthesia were simulated in vitro by gassing a suspension of SYM with a gas mixture of 1.5 and 3% (by vol.) of [14C]halothane in N2 at 37°C. The uptake of halothane into SYM as determined by radioactivity measurements was 31 and 73 mmol per mol membrane lipid or 4 and 9 mg per g membrane, respectively. The same concentrations of halothane in the membrane suspensions increased membrane fluidity of SYM significantly as shown by measurements of fluorescence depolarisation of in‐corporated DPH. At halothane concentrations corresponding to 1.5 and 3% (by vol.) in the gas phase the degradation of sphingomyelin by membrane‐bound neutral sphingomyelinase of SYM was stimulated by 11 and 57% of controls, respectively. These results are discussed in relation to the anaesthetic potential of halothane. Key words: Synaptosomal plasma membranes‐Membrane‐bound neutral sphingomyelinase‐Membrane fluidity‐Halothane‐Clinical concentrations.