Figure 4.7 The effect of perfusion of the microdialysis probe with a medium containing a depolarising (80 mM) concentration of K+, or Ca2+-free medium, for the periods indicated by the bars. The graph shows efflux of noradrenaline in the frontal cortex of anaesthetised rats. Increasing the concentration of K+ in the medium infused via the probe increases noradrenaline efflux whereas removing Ca2+ reduces it is needed for analysis: i.e. by the sensitivity of the assay system. It is acknowledged that the solutes are not in equilibrium with the CSF outside the probe. In any case, the efficiency of the probe membrane limits the net influx (or efflux) of solutes to about 1020% of the theoretical maximum. It should also be borne in mind that the microdialysis probe is not sampling the transmitter in the synapse: only that transmitter which escapes metabolism in, or reuptake from, synapses will migrate towards the probe. In the drug-free state, any change in the transmitter concentration in the dialysis samples is usually assumed to indicate a change in its rate of release from nerve terminals; this is supported by the spontaneous efflux of transmitters being Ca2+-dependent and K+-sensitive (Fig. 4.7). However, efflux does not always reflect release rate, especially if experimental interventions (e.g. infusion of monoamine uptake inhibitors) interfere with the clearance of transmitter from the synapse (Fig. 4.8).
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