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J Neurophysiol 89: 2778-2783, 2003. First published January 22, 2003; doi:10.1152/jn.01038.2002
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J Neurophysiol (May 1, 2003). 10.1152/jn.01038.2002
Submitted on Submitted 15 November 2002; accepted in final form 20 January 2003

A Slow Fraction of Mg2+ Unblock of NMDA Receptors Limits Their Contribution to Spike Generation in Cortical Pyramidal Neurons

Mariana Vargas-Caballero and Hugh P. C. Robinson

Department of Physiology, University of Cambridge, Downing Street, CB2 3EG, Cambridge, United Kingdom

Vargas-Caballero, Mariana and Hugh P. C. Robinson. A Slow Fraction of Mg2+ Unblock of NMDA Receptors Limits Their Contribution to Spike Generation in Cortical Pyramidal Neurons. J. Neurophysiol. 89: 2778-2783, 2003. The timing of voltage-dependent removal of Mg2+ block of N-methyl-D-aspartate receptors (NMDARs) is potentially critical for determining their nonlinear contribution to excitability. Here, we measure the kinetics of NMDAR unblock in nucleated patch and whole cell recordings of rat cortical pyramidal neurons during depolarizing voltage steps. At room temperature, the unblock showed a very fast component (tau  < 1 ms) and a slower component (tau  = 14-23 ms in nucleated patches). The slow component accounted for half of the current at +40 mV and its amplitude and time constant showed some voltage dependence. Blocking with hyperpolarization was very fast (tau  < 200 µs). Voltage-clamp with action potential waveforms, at both room temperature and at 33°C, showed that the rising phase of single fast action potentials unblocks far less NMDAR current than expected from the stationary voltage dependence, while a large amplitude of current is uncovered during the upstroke of slow calcium action potentials. The repolarization of fast sodium action potentials uncovers an NMDAR tail current, much bigger than the stationary level of current.




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