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A slow fraction of Mg2+ unblock of NMDA receptors limits their contribution to spike generation in cortical pyramidal neurons

A slow fraction of Mg2+ unblock of NMDA receptors limits their contribution to spike generation in cortical pyramidal neurons
A slow fraction of Mg2+ unblock of NMDA receptors limits their contribution to spike generation in cortical pyramidal neurons
The timing of voltage-dependent removal of Mg(2+) 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 micros). Voltage-clamp with action potential waveforms, at both room temperature and at 33 degrees 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.
0022-3077
2778-2783
Vargas-Caballero, Mariana
de2178ac-77fd-4748-9fe5-109ab8ad93e1
Robinson, Hugh P.C.
9e490d5e-ab13-42f4-bee8-8dc5312bad83
Vargas-Caballero, Mariana
de2178ac-77fd-4748-9fe5-109ab8ad93e1
Robinson, Hugh P.C.
9e490d5e-ab13-42f4-bee8-8dc5312bad83

Vargas-Caballero, Mariana and Robinson, Hugh P.C. (2003) A slow fraction of Mg2+ unblock of NMDA receptors limits their contribution to spike generation in cortical pyramidal neurons. Journal of Neurophysiology, 89 (5), 2778-2783. (doi:10.1152/jn.01038.2002). (PMID:12611983)

Record type: Article

Abstract

The timing of voltage-dependent removal of Mg(2+) 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 micros). Voltage-clamp with action potential waveforms, at both room temperature and at 33 degrees 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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Published date: 22 January 2003
Organisations: Centre for Biological Sciences

Identifiers

Local EPrints ID: 348677
URI: http://eprints.soton.ac.uk/id/eprint/348677
ISSN: 0022-3077
PURE UUID: d3a260bc-fb47-4a2f-8c91-d60f6060b0e7
ORCID for Mariana Vargas-Caballero: ORCID iD orcid.org/0000-0003-2326-4001

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Date deposited: 13 May 2013 13:42
Last modified: 17 Dec 2019 01:38

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