Role of GABAA and GABAC Receptors in the Biphasic GABA Responses in Neurons of the Rat Major Pelvic Ganglia

1 Department of Physiology and 2 Department of Urology, Kurume University School of Medicine, Kurume 830-0011, Japan Akasu, Takashi, Yoshikazu Munakata, Masashi Tsurusaki, and Hiroshi Hasuo. Role of GABA A and GABA C Receptors in the Biphasic GABA Responses in Neurons of the Rat Major Pelvic Ganglia. J. Neurophysiol. 82: 1489-1496, 1999. The role of -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