273P METHOHEXITONE INHIBITION OF K+-STIMULATED RELEASE OF [3H]NORADRENALINE FROM MINI-SLICES OF RAT CEREBRAL CORTEX IS DEPENDENT ON K+ CONCENTRATION C.A. Jones & K.M. Silvers, Department of Biomedical Science, University of Sheffield, Sheffield SIO 2TN. Previous experiments have shown high concentrations of barbiturate anaesthetics to cause a dose-dependent inhibition of K+stimulated release of [H]noradrenaline from minislices of rat cerebral cortex (Jones & Symington, 1990). The present study investigated whether the response to methohexitone would depend on the K+ stimulus used. Minislices (350 sum x 350 zm) of rat cerebral cortex loaded with ["Hlnoradrenaline were superfused with a modified Krebsphosphate solution containing pargyline (10-l M) and desipramine (10-7 M) at 500 !d min-. After equilibration fractions of superfusate were collected at 2 min intervals. Release of pH]noradrenaline was stimulated by 2 min pulses of high K+ Krebs solution introduced at 6 and 30 min. Methohexitone was introduced at 18 min. pH]Noradrenaline efflux was estimated by liquid scintillation counting. Results were calculated as the S2/Si ratio (where S2 and SI are the increase in release over basal observed during the 10 min period after each K+ stimulus, expressed as a fraction of the total tissue content of [3H]noradrenaline). These are summarised in Table 1 as percentage of the S2/S ratio for methohexitone-free controls. Effect of K+ concentration on response to methohexitone Table 1 10-4 3 x 10-5 Methohexitone concentration (M): 10-5 **52 ± 8 88 ± 9 94 ± 9 12.5 mM K+ **42 ± 4 **72 ± 4 93 ± 5 25 mM K+ **42± 6 *69 5 5 *70 50 mM K+ Results are % control, mean ± s.e. mean, n = 7-27, *p