Title: Role of GABA<sub>A</sub> and GABA<sub>C</sub> Receptors in the Biphasic GABA Responses in Neurons of the Rat Major Pelvic Ganglia
Abstract: The role of γ-aminobutyric acid-A (GABA A ) and GABA C receptors in the GABA-induced biphasic response in neurons of the rat major pelvic ganglia (MPG) were examined in vitro. Application of GABA (100 μM) to MPG neurons produced a biphasic response, an initial depolarization (GABA d ) followed by a hyperpolarization (GABA h ). The input resistance of the MPG neurons was decreased during the GABA d , whereas it was increased during the GABA h . The GABA d could be further separated into the early component (early GABA d ) with a duration of 27 ± 5 s (mean ± SE; n = 11) and the late component (late GABA d ) with a duration of 109 ± 11 s ( n = 11). The duration of the GABA h was 516 ± 64 s ( n = 11). The effects of GABA (5–500 μM) in producing the depolarization and the hyperpolarization were concentration-dependent. GABA (5–30 μM) induced only late depolarizations. The early component of the depolarization appeared when the concentration of GABA was >50 μM. Muscimol produced only early depolarizing responses. Baclofen (100 μM) had no effect on the membrane potential and input resistance of MPG neurons. Bicuculline (60 μM) blocked the early GABA d but not the late GABA d and the GABA h . Application of picrotoxin (100 μM) with bicuculline (60 μM) blocked both the late GABA d and the GABA h . CGP55845A (3 μM), a selective GABA B receptor antagonist, did not affect the GABA-induced responses. cis-4-Aminocrotonic acid (CACA, 1 mM) and trans-4-aminocrotonic acid (TACA, 1 mM), selective GABA C receptor agonists, produced late biphasic responses in the MPG neurons. The duration of the CACA responses was almost the same as those of the late GABA d and GABA h obtained in the presence of bicuculline. Imidazole-4-acetic acid (I4AA, 100 μM), a GABA C receptor antagonist, depressed the late GABA d and the GABA h but not the early GABA d . I4AA (100 μM) and picrotoxin (100 μM) also suppressed the biphasic response to CACA. The early GABA d and the late GABA d were reversed in polarity at −32 ± 3 mV ( n = 7) and −38 ± 2 mV ( n = 4), respectively, in the Krebs solution. The reversal potential of the GABA h was −34 ± 2 mV ( n = 4) in the Krebs solution. The reversal potentials of the late GABA d and the GABA h shifted to −20 ± 3 mV ( n = 5) and −22 ± 3 mV ( n = 5), respectively, in 85 mM Cl − solution. These results indicate that the late GABA d and the GABA h are mediated predominantly by bicuculline-insensitive, picrotoxin-sensitive GABA receptors, GABA C (or GABA AOr ) receptors, in neurons of the rat MPG.
Publication Year: 1999
Publication Date: 1999-09-01
Language: en
Type: article
Indexed In: ['crossref', 'pubmed']
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Cited By Count: 22
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