Axotomy-induced change in the properties of (S)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate receptor channels in rat motoneurons

Properties of (S)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMP A) receptor channels were studied in fluorescence-labelled control and axot omized motoneurons in spinal cord slices using a patch-clamp technique, Axo tomy performed on the third postnatal day resulted in motoneuron death. App lication of AMPA or kainate induced large whole-cell currents, but outside- out patches isolated from control motoneurons were either unresponsive or d isplayed only single-channel activity in response to rapid application of A MPA. Measurement of AMPA receptor channel openings in outside-out patches r evealed multiple single-channel conductance levels: 12.2 +/- 1.0, 21.9 +/- 1.5 and 32.6 +/- 3.2 pS. In control motoneurons dialysed with spermine, the current-voltage relationship of responses induced by activation of AMPA re ceptor channels exhibited various degrees of inward rectification. The rect ification index, the ratio of responses at + 40 and -60 mV, was used to com pare the degree of inward rectification. The mean values of rectification i ndex of responses to focal application of AMPA and AMPA receptor-mediated e xcitatory postsynaptic currents induced by focal electric stimulation were 0.64 +/- 0.17 and 0.50 +/- 0.27, respectively. In axotomized motoneurons, t he degree of rectification was significantly less for both responses induce d by application of AMPA and for excitatory postsynaptic currents (0.91 +/- 0.09 and 0.95 +/- 0.12, respectively). Deactivation of AMPA receptors asse ssed from motoneuron excitatory postsynaptic currents at -70 mV was indepen dent of postnatal age, with tau(fast) = 0 88 +/- 0.35 ms (A(fast) = 78.2 +/ - 11.8%) and tau(slow) = 6.3 +/- 3.2 ms. In axotomized motoneurons, the dec ay time constants of excitatory postsynaptic currents were similar, tau(fas t) = 0.91 +/- 0.42 ms (A(fast) = 85.8 +/- 12.6%) and tau(slow) = 5.9 +/- 3. 4 ms. However, the mean amplitude of excitatory postsynaptic currents was o nly 43% of the amplitude recorded in control motoneurons. The results show that the current induced by activation of AMPA receptors i n neonatal motoneurons is mediated by opening of both Ca2+-permeable and Ca 2+-impermeable channels. As a result of axotomy, an experimental model of n eurodegeneration, AMPA receptor channels in injured motoneurons destined to die become predominantly Ca2+ impermeable. These findings suggest phenotyp ic control of AMPA receptor channel properties, presumably by affecting the ir subunit composition. (C) 2000 IBRO. Published by Elsevier Science Ltd. A ll rights reserved.