Maximum likelihood fitting of single channel NMDA activity with a mechanism composed of independent dimers of subunits.
Steady-state single channel activity from NMDA receptors was recorded at a range of concentrations of both glutamate and glycine. The results were fitted with several plausible mechanisms that describe both binding and gating. The mechanisms we have tested were based on our present understanding of receptor structure, or based on previously proposed mechanisms for these receptors. The steady-state channel properties appear to have virtually no dependence on the concentration of either ligand, other than the frequency of channel activations. This limited the ability to discriminate detail in the mechanism, and, along with the persistence of open-shut correlations in high agonist concentrations, suggests that NMDA channels, unlike other neurotransmitter receptors, cannot open unless all binding sites are occupied. As usual for analyses of NMDA channels, the applicability of our results to physiological observations is limited by uncertainties in synaptic zinc and hydrogen ion concentrations, both of these being known to affect the receptor. The mechanism that we propose, on the basis of steady-state single channel recordings, predicts with fair accuracy the apparent open and shut-time distributions in different concentrations of agonists, correlations between open and shut times, and both the rising and falling phases of the macroscopic response to concentration jumps, and can therefore account for the main features of synaptic currents.
Schorge
Stephanie
S
Department of Pharmacology, UCL, London WC1E 6BT, UK.
Elenes
Sergio
S
Colquhoun
David
D
D000818:Animals; D003627:Data Interpretation, Statistical; D004492:Edetic Acid / Q000494:pharmacology; D005260:Female; D018698:Glutamic Acid / Q000494:pharmacology / Q000502:physiology; D005998:Glycine / Q000494:pharmacology / Q000502:physiology; D006863:Hydrogen-Ion Concentration; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology*; D007473:Ion Channels / Q000737:chemistry* / Q000187:drug effects / Q000502:physiology*; D016013:Likelihood Functions; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D018408:Patch-Clamp Techniques; D011336:Probability; D011485:Protein Binding; D017470:Receptors, Glutamate / Q000502:physiology; D018009:Receptors, Glycine / Q000502:physiology; D016194:Receptors, N-Methyl-D-Aspartate / Q000737:chemistry* / Q000187:drug effects / Q000502:physiology*; D015290:Second Messenger Systems / Q000502:physiology; D013997:Time Factors; D014982:Xenopus laevis
D007473:Ion Channels; D017470:Receptors, Glutamate; D018009:Receptors, Glycine; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid; D004492:Edetic Acid; D005998:Glycine