The Journal of Neurophysiology Vol. 82 No. 3 September 1999, pp. 1489-1496
Copyright ©1999 by the American Physiological Society

Role of GABA_A and GABA_C Receptors in the Biphasic GABA Responses in Neurons of the Rat Major Pelvic Ganglia

 ¹Department of Physiology and  ²Department 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) 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.