The attenuation of GABA sensitivity in the maturing myelin-deficient rat optic nerve.
GABA (gamma-aminobutyric acid) can modulate axonal excitability by activating GABAA receptors on some central nervous system axons. The effects of GABA on optic nerve axons decrease significantly during the course of myelination, suggesting that myelination may influence changes in GABA sensitivity. To test this hypothesis, we compared the depolarizing effect of GABA and the GABAA-receptor agonist, muscimol, on optic nerves of myelin-deficient (MD) rats and their unaffected siblings using a modified sucrose-gap technique. Optic nerves from both control and MD rats displayed relatively large GABA-induced depolarizations when studied at an early postnatal period. In both the control and MD rats, the GABA uptake inhibitor nipecotic acid led to a distinct depolarization suggesting endogenous release of GABA. Although the GABA-induced depolarization in the MD rat was significantly greater than that in the control rat at the third postnatal week, the response in the MD rat attenuated with maturation. These results demonstrate that the attenuation of the depolarization induced by GABA and nipecotic acid seen in the normal optic nerve also occurs in the MD rat optic nerve. This suggests that the attenuation of optic nerve sensitivity to GABA is not the result of myelination or interaction with myelin-associated proteins.
Department of Neurology, Yale University School of Medicine, New Haven, CT 06510.
J Y
JY
Lim
D A
DA
Utzschneider
K
K
Sakatani
J D
JD
Kocsis
D000200:Action Potentials / Q000187:drug effects; D000375:Aging / Q000502:physiology; D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D066298:In Vitro Techniques; D009118:Muscimol / Q000494:pharmacology; D009186:Myelin Sheath / Q000502:physiology*; D009557:Nipecotic Acids / Q000494:pharmacology; D009900:Optic Nerve / Q000187:drug effects / Q000254:growth & development / Q000502:physiology*; D011392:Proline / Q000031:analogs & derivatives*; D051381:Rats; D011922:Rats, Mutant Strains; D011963:Receptors, GABA-A / Q000502:physiology; D012016:Reference Values; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
D009557:Nipecotic Acids; D011963:Receptors, GABA-A; C030278:nipecotic acid; D009118:Muscimol; D005680:gamma-Aminobutyric Acid; D011392:Proline; C010983:homoproline; D001640:Bicuculline