Presynaptic and postsynaptic GABAB receptors of neocortical neurons of the rat in vitro: Differences in pharmacology and ionic mechanisms

✍ Scribed by Rudolf A. Deisz; Jean-Marie Billard; Walter Zieglgänsberger

• Publisher: John Wiley and Sons
• Year: 1997
• Tongue: English
• Weight: 143 KB
• Volume: 25
• Category: Article
• ISSN: 0887-4476
• DOI: 10.1002/(sici)1098-2396(199701)25:1<62::aid-syn8>3.0.co;2-d

✦ Synopsis

The properties of pre-and postsynaptic GABA B receptors were investigated with intracellular recordings from rat neocortical neurons in vitro. An antagonist of the GABA B receptor (CGP 35348) and ions or drugs interfering with GABA B receptor-mediated K 1 conductance (Ba 21 , QX 314) were employed to delineate possible differences. CGP 35348 reduced the conductance of the late inhibitory postsynaptic potential (IPSP B ) in a dose-dependent manner. Neither the early GABA A receptormediated inhibitory postsynaptic potential (IPSP A ), nor resting membrane potential or direct excitability, were consistently affected by CGP 35348. Bath application of 100 µmol/l Ba 21 decreased IPSP B conductance to about 40% and increased IPSP A conductance to 130% of control. The depression of a second IPSP by a pair of stimuli (paired pulse depression, or PPD) was used as an index for presynaptic GABA B receptor activation. Neither CGP 35348 nor Ba 21 exerted significant effects on the PPD at intervals of 400 msec. The dependence of PPD on the latency of the interval of the stimulus pair was investigated after intracellular application of QX 314 had virtually abolished the IPSP B . Decreasing the stimulus interval from 500 msec to 100 msec revealed a stronger depression of the second IPSP A . Application of CGP 35348 alleviated PPD for stimulus intervals below 300 msec. The data indicate a distinct pharmacological difference between pre-and postsynaptic GABA B receptors. Moreover, we suggest that two temporally distinct presynaptic GABA B receptor effects contribute to PPD: a short-lasting effect, sensitive to CGP 35348, and a long-lasting effect, insensitive to CGP 35348. The latter is insensitive to Ba 21 , implying that this component is not associated with a K 1 conductance mechanism.