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Journal of Neuroscience, Vol 6, 2290-2297, Copyright © 1986 by Society for Neuroscience
Actions of pentobarbital on rat brain receptors expressed in Xenopus oocytes
I Parker, CB Gundersen and R Miledi
Functional receptor channels activated by GABA and other neurotransmitters
were "transplanted" from rat brain to Xenopus oocytes by injecting the
oocytes with total poly(A)+ mRNA isolated from rat or chick brain. Membrane
currents elicited in the oocyte by GABA inverted polarity at about the
chloride equilibrium potential (ca. -25 mV). Pentobarbital potentiated the
GABA-activated currents, without appreciably changing the reversal
potential or form of the current- voltage relationship. At low (less than
10(-5) M) concentrations of GABA, pentobarbital (100 microM) potentiated
the responses by a factor of 10 or more, but responses to high (ca. 1 mM)
concentrations of GABA were almost unchanged. Half-maximal activation of
the response was obtained with about 3 X 10(-5) M GABA when applied alone
and with about 4 X 10(-6) M GABA when applied together with 100 microM
pentobarbital. At low doses of GABA, the size of the current increased as
the 1.4th power of GABA concentration, but this relationship became nearly
linear in the presence of pentobarbital. The potentiation of the GABA
response increased linearly with concentrations of pentobarbital up to
about 300 microM, reaching a maximum of about 50-fold. At higher
concentrations of pentobarbital, the response to GABA declined. Relaxations
of GABA- activated currents following voltage steps became slower in the
presence of pentobarbital, suggesting that the open life-time of the
channels was prolonged. In addition to actions on GABA-activated currents,
pentobarbital itself elicited a small membrane current that inverted
polarity at a potential (-10 mV) more positive than the GABA- activated
current.(ABSTRACT TRUNCATED AT 250 WORDS)
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