Developmental alteration in GABAA receptor structure and physiological properties in cultured cerebellar granule neurons.
Although we now have extensive knowledge about the GABAA receptor subunits determining benzodiazepine modulation of channel function, little is known about subunits influencing other modulatory sites on the GABAA receptor-chloride channel complex. We have identified a developmental change in subunit composition of the GABAA receptor in cultured cerebellar granule neurons that eliminates benzodiazepine-mediated enhancement of GABA responses and alters modulation by a substituted gamma-butyrolactone. Based on data from sequential PCR experiments, we mimicked the functional properties of early and mature receptors with heterologous expression of specific subunit combinations. This report describes one of the most extensive cell- and site-specific developmental changes for an ion channel seen to date.
Mathews
G C
GC
Medical Scientist Training Program, St. Louis Children's Hospital, Missouri 63110.
Bolos-Sy
A M
AM
Holland
K D
KD
Isenberg
K E
KE
Covey
D F
DF
Ferrendelli
J A
JA
Rothman
S M
SM
D015107:4-Butyrolactone / Q000494:pharmacology; D000818:Animals; D001483:Base Sequence; D001569:Benzodiazepines / Q000494:pharmacology; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology*; D002707:Chlordiazepoxide / Q000494:pharmacology; D018118:Chloride Channels / Q000502:physiology; D004357:Drug Synergism; D005260:Female; D015870:Gene Expression; D008969:Molecular Sequence Data; D009474:Neurons / Q000502:physiology*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018079:Receptors, GABA / Q000737:chemistry* / Q000235:genetics / Q000502:physiology*; D013997:Time Factors; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D018118:Chloride Channels; D012333:RNA, Messenger; D018079:Receptors, GABA; D001569:Benzodiazepines; D005680:gamma-Aminobutyric Acid; D002707:Chlordiazepoxide; D015107:4-Butyrolactone