AMPA receptor-mediated miniature synaptic calcium transients in GluR2 null mice.
AMPA-type glutamate receptors are normally Ca(2+) impermeable due to the expression of the GluR2 receptor subunit. By using GluR2 null mice we were able to detect miniature synaptic Ca(2+) transients (MSCTs) associated with AMPA-type receptor-mediated miniature synaptic currents at single synapses in primary cortical cultures. MSCTs and associated Ca(2+) transients were monitored under conditions that isolated responses mediated by AMPA or N-methyl-D-aspartate (NMDA) receptors. As expected, addition of the antagonist 6-cyano-7-nitroquinoxalene-2,3-dione (CNQX, 3 microM) blocked the AMPA receptor-mediated MSCTs. Voltage-gated Ca(2+) channels did not contribute to AMPA MSCTs because CdCl(2) (0.1-0.2 mM) did not significantly alter the frequency or the amplitude of the MSCTs. The amplitude of AMPA MSCTs appeared to be regulated independently from event frequency since the two measures were not correlated (R = 0.023). Synapses were identified that only expressed MSCTs attributed to either NMDA or AMPA receptors. At synapses with only NMDA responses, MSCT amplitude was significantly lower (by 40%) than synapses expressing both NMDA and AMPA responses. At synapses that showed MSCTs mediated by both AMPA and NMDA receptors, the amplitude of the transients in each condition was positively correlated (R = 0.94). Our results suggest that when AMPA and NMDA receptors are co-expressed at synapses, mechanisms exist to ensure proportional scaling of each receptor type that are distinct from the presynaptic factors controlling the frequency of miniature release.
Wang
Sabrina
S
Kinsmen Laboratory, Department of Psychiatry, University of British Columbia, Vancouver, British Columbia V6T 1Z3.
Jia
Zhengping
Z
Roder
John
J
Murphy
Timothy H
TH
D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000818:Animals; D019256:Cadmium Chloride / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D004594:Electrophysiology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout / Q000235:genetics; D018091:Receptors, AMPA / Q000172:deficiency* / Q000235:genetics / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology; D013569:Synapses / Q000378:metabolism*
D018691:Excitatory Amino Acid Antagonists; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D019256:Cadmium Chloride; C104722:glutamate receptor ionotropic, AMPA 2; D002118:Calcium