Glycine receptors involved in synaptic transmission are selectively regulated by the cytoskeleton in mouse spinal neurons.
Using whole cell patch-clamp recordings, we examined the effect of colchicine, a microtubule disrupter, on the properties of glycine receptors (GlyRs) in cultured spinal cord neurons. Confocal microscopy revealed that colchicine treatment effectively altered microtubule bundles and neuronal morphology. Application of colchicine via the culture media or the patch-pipette, however, did not affect the whole cell current rundown (73 +/- 6% of control after 1 h), the sensitivity of the GlyR to glycine (EC(50) = 29 +/- 1 microM), or strychnine inhibition (47 +/- 5% of control after 100 nM strychnine). On the other hand, colchicine dialyzed for 25 min via the patch pipette selectively reduced the quantal amplitude of spontaneous glycinergic miniature inhibitory postsynaptic currents (mIPSCs) to 68 +/- 5% of control. This effect was specific for GlyRs since synaptic events mediated by alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and GABA(A) receptors were unchanged. In conclusion, this study indicates that microtubules can regulate the function of GlyRs involved in inhibitory synaptic transmission.
van Zundert
Brigitte
B
Department of Physiology, University of Concepción, Concepcion, Chile.
Alvarez
Francisco J
FJ
Yevenes
Gonzalo E
GE
Cárcamo
Juan G
JG
Vera
Juan Carlos
JC
Aguayo
Luis G
LG
D000818:Animals; D002478:Cells, Cultured; D003078:Colchicine / Q000494:pharmacology; D003599:Cytoskeleton / Q000187:drug effects / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005998:Glycine / Q000494:pharmacology; D018684:Glycine Agents / Q000494:pharmacology; D017136:Ion Transport / Q000187:drug effects; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008870:Microtubules / Q000187:drug effects / Q000378:metabolism; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D018009:Receptors, Glycine / Q000378:metabolism*; D013116:Spinal Cord / Q000166:cytology / Q000196:embryology / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*
D018691:Excitatory Amino Acid Antagonists; D018684:Glycine Agents; D018009:Receptors, Glycine; D003078:Colchicine; D005998:Glycine