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First published online on August 1, 2003.
Copyright © 2003 by The Physiological Society
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jphysiol.2003.047415v1
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Received May 16, 2003
Revised June 16, 2003
Accepted after revision July 31, 2003

CONDUCTANCE OF GABAA CHANNELS ACTIVATED BY PENTOBARBITONE IN HIPPOCAMPAL NEURONS FROM NEWBORN RATS

Mansoureh Eghbali1, Bryndis Birnir2, and Peter W Gage3*

1 UCLA
2 University of Lund
3 John Curtin School of Medical Research

* To whom correspondence should be addressed. E-mail: peter.gage{at}anu.edu.au.

Neurons were obtained from the CA1 region of the hippocampus of newborn rats and maintained in culture. Channels were activated by pentobarbitone in cell-attached, inside-out or outside-out patches, normally by applying pentobarbitone in flowing bath solution. Currents were outwardly rectifying and blocked by bicuculline, properties of GABAA channels in these cells. Maximum channel conductance increased as pentobarbitone concentration was increased to 500 µM but conductance then decreased as pentobarbitone concentration was raised further. The best fit of a Hill-type equation to the relationship between maximum channel conductance and pentobarbitone concentration (up to 500 µM) gave an EC50 of 41 µM, a maximum conductance of 36 pS and a Hill co-efficient of 1.6. Bicuculline decreased the maximum conductance of channels activated by pentobarbitone. The effect on channel conductance had an IC50 of 224 µM. Diazepam increased channel conductance with a maximum effect being obtained with 1 µM diazepam. Diazepam (1 µM) decreased the EC50 of the pentobarbitone effect on channel conductance from 41 µM to 7.2 µM and increased maximum conductance to 72 pS. We conclude that GABAA channel conductance is related to the concentration of the allosteric agonist, pentobarbitone.


Key words: aminobutyric acid (GABA) • Barbiturate • Channels







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