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SUMMARY1. Depolarizations to L-glutamate, applied locally by microionophoresis to the extrajunctional membrane of locust extensor tibiae muscle fibres and measured either in current clamp or voltage clamp, increased in amplitude for equivalent doses of glutamate following chronic denervation of the muscle.2. A two-pulse method was used to examine recovery from desensitization of junctional and extrajunctional receptors. A 'response ratio', i.e. the amplitude of response to the second (test) of a pair of glutamate pulses over the response to the first (control), was determined as a function of the time interval between the pulses. The 'response ratio' for extrajunctional depolarizations of innervated fibres increased exponentially with pulse interval, with a time constant of 15-6 + 4-7 sec (n = 11). Recovery of extrajunctional receptor populations from desensitization was accelerated after denervation. The recovery kinetics for responses from fibres 6-22 days after denervation were generally described by two exponential terms, with time constants in the range 0.5-10 sec which were inversely related to the glutamate sensitivity of the extrajunctional membrane. For junctional receptors on both innervated and denervated fibres the recovery kinetics were described by a single exponential with a time constant of 0.2-1 sec.3. The results suggest that the increased extrajunctional glutamate sensitivity which occurs after denervation results from the 'appearance' of glutamate receptors with properties similar to those found at the post-junctional membrane on locust muscle fibres.

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SUMMARY1. The desensitization, by ionophoretically and bath-applied L-glutamate and agonists, of excitatory post-junctional receptor populations on locust extensor tibiae muscle was investigated.2. The kinetics of onset of and recovery from desensitization were determined ionophoretically either with trains ofglutamate/agonist pulses ofdifferent frequencies ('conditioning trains') followed by a single 'test' pulse at different intervals after cessation of the conditioning train or with trains of constant frequency drug pulses superimposed upon steady 'conditioning' doses. Both methods gave quantitatively similar results.3. For approximately equipotent doses, L-glutamate and agonists produced different rates of desensitization onset. Qualitatively similar results were obtained when changes in input conductance of single muscle fibres were measured during bath application of the amino acids.4. The time courses of recovery from desensitization for receptor populations activated by glutamate and agonists could be described adequately by single exponential and were independent of the concentration of amino acid except when desensitization exceeded ca. 90 %.5. The rate of recovery from desensitization was different for each agonist.

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