Inhibitory effect of baclofen on GABA-induced depolarization and GABA-activated current in primary sensory neurons.
It has been established that GABAA and GABAB receptors can exist separately and/or co-exist in the membrane of dorsal root ganglion neurons. In our previous investigation it has been shown that co-existence of these two kinds of receptors is about 80% of the neurons examined (20/25). The present study was aimed to explore whether the activation of these two kinds of receptors could interact with each other using intracellular and whole-cell patch-clamp recordings. Baclofen, a specific GABAB receptor agonist, was found to exert negative modulatory effects on the responses mediated by GABAA receptor. In experiments with intracellular recording, GABA (0.3-1000 microM)- and muscimol (100-1000 microM)-induced depolarization was attenuated markedly and reversibly by preapplication of baclofen (100 microM) (15/21 and 17/21, respectively). In whole-cell patch-clamp recordings GABA (100 microM) and two specific GABAA receptor agonists, muscimol (10 microM) and isoguvacine (50 microM), activated currents were inhibited markedly by preapplication of baclofen 30 s or more and the inhibition was concentration dependent (1-100 microM baclofen) and reversible. The possible mechanisms underlying the inhibition by baclofen of the responses mediated by GABAA receptor and the physiological significance implicated are discussed.
Si
J Q
JQ
Research Center of Experimental Medicine, Tongji Medical University, Wuhan, People's Republic of China.
Li
Z W
ZW
Hu
H Z
HZ
Zhou
X P
XP
Guan
B C
BC
D000818:Animals; D001418:Baclofen / Q000494:pharmacology*; D004553:Electric Conductivity; D004594:Electrophysiology; D005260:Female; D018755:GABA Agonists / Q000494:pharmacology*; D007539:Isonicotinic Acids / Q000494:pharmacology; D008297:Male; D009118:Muscimol / Q000494:pharmacology; D009475:Neurons, Afferent / Q000187:drug effects* / Q000502:physiology*; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
D018755:GABA Agonists; D007539:Isonicotinic Acids; D009118:Muscimol; D005680:gamma-Aminobutyric Acid; D001418:Baclofen; C015300:isoguvacine