Effect of PSD-95/SAP90 and/or PSD-93/chapsyn-110 deficiency on the minimum alveolar anesthetic concentration of halothane in mice.
BACKGROUND
The authors have previously shown that the clinically relevant concentrations of inhalational anesthetics dose-dependently inhibit the postsynaptic density protein (PSD)-95, Dlg, and ZO-1 domain-mediated protein interactions between N-methyl-d-aspartate receptors and PSD-95/synaptic-associated protein (SAP) 90 or PSD-93/Chapsyn-110 and that the knockdown of spinal PSD-95/SAP90 significantly reduces the minimum alveolar concentration (MAC) for isoflurane in rats.


METHODS
The authors designed antisense oligodeoxynucleotides based on the mouse PSD-95/SAP90 and PSD-93/Chapsyn-110 messenger RNAs that correspond to their PSD-95, Dlg, and ZO-1 domain nucleotides and can specifically knock down the respective proteins. The authors intrathecally injected antisense oligodeoxynucleotides into wild-type and PSD-93/Chapsyn-110 knockout mice to investigate the effect of PSD-95/SAP90 and/or PSD-93/Chapsyn-110 deficiency on halothane anesthesia.


RESULTS
Both PSD-95/SAP90 and PSD-93/Chapsyn-110 antisense oligodeoxynucleotides caused a dose-dependent and significant reduction in the MAC of halothane in wild-type mice. The intrathecal injection of PSD-95/SAP90 antisense oligodeoxynucleotide at different doses (25 and 50 microg) reduced halothane MAC by 40 and 55%, respectively, and intrathecal injection of PSD-93/Chapsyn-110 antisense oligodeoxynucleotide at different doses (12 and 24 microg) reduced halothane MAC by 25 and 53%, respectively. The PSD-95/SAP90 antisense oligodeoxynucleotide showed similar effect on halothane MAC in wild-type and PSD-93/Chapsyn-110 knockout mice, suggesting that the combination of PSD-95/SAP90 knockdown with PSD-93/Chapsyn-110 deletion did not have an additive effect on halothane anesthesia.


CONCLUSIONS
The current results indicate that PSD-95/SAP90 and PSD-93/Chapsyn-110 are involved in the molecular mechanisms of halothane anesthesia and that the functional role of PSD-95/SAP90 in halothane anesthesia is not enhanced after PSD-93/Chapsyn-110 deletion.
Tao
Feng
F
Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Skinner
John
J
Yang
Ya
Y
Johns
Roger A
RA
D018685:Anesthetics, Inhalation / Q000008:administration & dosage / Q000378:metabolism*; D000818:Animals; D000076122:Disks Large Homolog 4 Protein; D051528:Guanylate Kinases; D006221:Halothane / Q000008:administration & dosage / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors / Q000172:deficiency* / Q000235:genetics; D008297:Male; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000172:deficiency* / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009043:Motor Activity / Q000235:genetics; D020319:Oligodeoxyribonucleotides, Antisense / Q000008:administration & dosage; D011650:Pulmonary Alveoli / Q000187:drug effects / Q000378:metabolism*
D018685:Anesthetics, Inhalation; D000076122:Disks Large Homolog 4 Protein; C501447:Dlg4 protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D020319:Oligodeoxyribonucleotides, Antisense; C501445:Dlg2 protein, mouse; D051528:Guanylate Kinases; D006221:Halothane