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

Properties of (S)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptor channels were studied in fluorescence-labelled control and axotomized motoneurons in spinal cord slices using a patch-clamp technique, Axotomy performed on the third postnatal day resulted in motoneuron death. Application of AMPA or kainate induced large whole-cell currents, but outside-out patches isolated from control motoneurons were either unresponsive or displayed only single-channel activity in response to rapid application of AMPA. Measurement of AMPA receptor channel openings in outside-out patches revealed 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 receptor channels exhibited various degrees of inward rectification. The rectification index, the ratio of responses at + 40 and -60 mV, was used to compare the degree of inward rectification. The mean values of rectification index of responses to focal application of AMPA and AMPA receptor-mediated excitatory postsynaptic currents induced by focal electric stimulation were 0.64 +/- 0.17 and 0.50 +/- 0.27, respectively. In axotomized motoneurons, the degree of rectification was significantly less for both responses induced by application of AMPA and for excitatory postsynaptic currents (0.91 +/- 0.09 and 0.95 +/- 0.12, respectively). Deactivation of AMPA receptors assessed from motoneuron excitatory postsynaptic currents at -70 mV was independent 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 decay time constants of excitatory postsynaptic currents were similar, tau(fast) = 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 only 43% of the amplitude recorded in control motoneurons. The results show that the current induced by activation of AMPA receptors in neonatal motoneurons is mediated by opening of both Ca2+-permeable and Ca2+-impermeable channels. As a result of axotomy, an experimental model of neurodegeneration, AMPA receptor channels in injured motoneurons destined to die become predominantly Ca2+ impermeable. These findings suggest phenotypic control of AMPA receptor channel properties, presumably by affecting their subunit composition. (C) 2000 IBRO. Published by Elsevier Science Ltd. All rights reserved.