ANESTHETICS MODULATE PHOSPHOLIPASE-C HYDROLYSIS OF MONOLAYER PHOSPHOLIPIDS BY SURFACE PRESSURE

Anesthetics are believed to produce anesthesia through the reversible inhibition of synaptic transmission but how this is accomplished is un known. Based on earlier studies of anesthetic-enzyme-phospholipid inte raction, we surmised that anesthetics may inhibit synaptic transmissio n by increasing synaptic membrane lateral pressure thereby inhibiting phospholipid hydrolysis, membrane transduction and synaptic transmissi on. As a first approximation towards investigating this concept, we hy pothesized that anesthetics modulate the rate of phospholipase C hydro lysis of a lipid monolayer through its effects on surface pressure. Th e relationship between the hydrolysis rate of a monolayer of dipalmito ylphosphatidylcholine [C-14-choline] (DPPC) by phospholipase C (Plase C) and monolayer surface pressure (SP) as altered by either halothane, isoflurane, or by physical compression at 37 degrees C was studied. T he decline in surface C-14-activity as the [C-14]choline diffuses into the Krebs-Ringer bicarbonate buffer aqueous subphase is estimated as the rate of DPPC hydrolysis measured by the initial slope method. DPPC hydrolysis was about 300 cpm/min and constant between SP of 0 to 20 d ynes/cm. Higher SP between 25 and 30 dyne/cm, whether induced by halot hane, isoflurane or physical compression, increased the rate of hydrol ysis by 5-fold to a peak rate of about 1600 cpm/min at 25-30 dynes/cm. Al a SP above 32 dynes/cm, DPPC hydrolysis abruptly ceased. We conclu de that anesthetics can reversibly inhibit synaptic transmission throu gh their effects on synaptic membrane lateral pressure. We also specul ate that membrane lateral pressure may be a highly sensitive means of controlling membrane function through alteration in membrane lipid com position, membrane enzyme activity, receptor affinity and ion channel permeability.