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J Neurophysiol (January 22, 2003). doi:10.1152/jn.01038.2002
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Submitted on November 15, 2002
Accepted on January 20, 2003

A slow component of voltage-dependent Mg2+ unblock of NMDA receptors limits their contribution to spike generation in cortical pyramidal neurons

Mariana Vargas-Caballero1* and Hugh P. C. Robinson1

1 Department of Physiology, University of Cambridge, Cambridge, United Kingdom

* To whom correspondence should be addressed. E-mail: mv229{at}cam.ac.uk.

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 depolarising 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 repolarisation of fast sodium action potentials uncovers an NMDAR tail current, much bigger than the stationary level of current.




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