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PubMed1991

gamma-Aminobutyric acid is a neuromodulator in sinus node of guinea pig heart.

A possible neurotransmitter role for gamma-aminobutyric acid (GABA) in the sinus node of guinea pig heart was examined. Among right atrium, left atrium, right ventricle, left ventricle, and sinus node, the highest amount of the endogenous GABA was found in the sinus node (1,240.6 +/- 120.8 nmol/g protein). The neuronal uptake of [3H]GABA was also the highest in the sinus node and kinetic analysis of the [3H]GABA uptake system in the sinus node showed one saturable component (Km = 17.3 microM, Vmax = 2.18 nmol.g protein-1.10 min-1). Autoradiography of [3H]GABA demonstrated heavy labeling of [3H]GABA in the nonmyelinated nerve fibers within the sinus node compared with findings in the atrial muscle. Electrical transmural stimulation evoked a Ca(2+)-dependent tetrodotoxin-sensitive release of [3H]GABA from the isolated sinus node preloaded with [3H]GABA in the presence of beta-alanine, thereby indicating that the [3H]GABA in the nerve is released from nerve terminals following electrical stimulation. These results provide evidence for the neuromodulator role of GABA in the sinus node of the guinea pig.

Animals↗
PubMed1981

SL 75 102 as a gama-aminobutyric acid agonist: experiments on dorsal root ganglion neurones in vitro.

1 In anticipation that centrally active gamma-aminobutyric acid (GABA)-mimetic drugs may be clinically useful, derivatives of GABA with an imine link (Schiff base) to a lipophilic carrier have recently been prepared. The present paper concerns the actions of [alpha(4-chlorophenyl)5-fluoro, 2-hydroxy benzilidene-amino]-4-butanoate Na+, SL 75 102. 2 To test one aspect of the GABA-mimetic properties of SL 75 102, this compound was compared with GABA for activity on intracellularly-recorded neurones in rat dorsal root ganglia in vitro. On these neurones GABA, administered either by microiontophoresis or direct into the superfusion medium, causes a depolarization, due to an increased chloride conductance, followed by a period of desensitization. 3 The actions of Sl 75 102 were in nearly all respects identical to those of GABA; parameters examined were the effects on membrane potential and input conductance, desensitization, dose-response characteristics and sensitivity to the GABA antagonists, bicuculline and picrotoxin. 4 SL 75 102 was less potent than GABA (mean relative potency 0.03:1). 5 SL 75 102 therefore appears to be a weak agonist at GABA receptors of these neurones.

Animals↗
PubMed1998

Gamma aminobutyric acid immunoreactivity in the mouse adrenal gland during postnatal development.

To understand the developing processes of gamma-aminobutyric acid (GABA)-containing chromaffin cells and nerve fibers in the mouse adrenal gland, we examined the tissues in various postnatal stages by immunohistochemistry using a GABA antibody. From birth until postnatal week 1, GABA-immunoreactivity was seen in very few nerve fibers, and in none of the chromaffin cells. At postnatal week 2, GABA-immunoreactivity appeared weakly in clusters of chromaffin cells and strongly in relatively numerous varicose nerve fibers. The immunoreactive nerve fibers were densely distributed in the small immunonegative chromaffin cells and large ganglion cells, but only sparsely so in the weak immunoreactive chromaffin cells. At postnatal week 3, the number of the immunoreactive chromaffin cells and nerve fibers further increased compared to that at postnatal week 2. The staining pattern of GABA-immunoreactive nerve fibers in the medullas was similar to that at postnatal week 2. From postnatal week 4 until postnatal week 8, the distribution and frequency of the immunoreactive chromaffin cells and nerve fibers were also similar to those at postnatal week 3. These results suggest that the expression of GABA in the chromaffin cells and in the nerve fibers of the mouse adrenal gland may be completed by postnatal week 3.

Adrenal Glands↗
PubMed1985

Prolactin in cerebrospinal fluid increases the synthesis and release of hypothalamic gamma-aminobutyric acid.

The effect of intracerebroventricularly (i.v.t.)-injected rat prolactin (2 micrograms/rat) on the function of tuberoinfundibular gamma-aminobutyric acid (GABA)ergic neurones was assessed in adult male rats by measuring the activity of glutamic acid decarboxylase (GAD) in the mediobasal hypothalamus (MBH) and the concentrations of GABA in hypophysial portal plasma and in the anterior pituitary gland. Fourteen hours after i.v.t. injection of rat prolactin the activity of GAD in the MBH was significantly (P less than 0.05) increased and it remained elevated for at least 16 h after injection. The mean concentrations of GABA in hypophysial portal plasma and in the anterior pituitary were twice those found in vehicle-treated controls 16 h after administration of rat prolactin; no significant effects were observed at earlier time-periods. A significant (P less than 0.01) and long-lasting decrease in endogenous plasma prolactin concentrations was detected 2 h after the i.v.t. injection of rat prolactin and the concentrations remained suppressed for up to 16 h. The present results are consistent with the concept that the activity of tuberoinfundibular GABAergic neurones is regulated, at least in part, by circulating prolactin. The ability of prolactin to accelerate the synthesis and release of GABA in the MBH might constitute a short loop feedback system by which the hormone regulates its own secretion.

Animals↗
PubMed1980

gamma-Aminobutyric acid and postganglionic sympathetic transmission in the pulmonary artery of the rabbit.

1 The effect of gamma-aminobutyric acid (GABA) on postganglionic sympathetic neurotransmission was studied in strips of the rabbit pulmonary artery. The strips were preincubated with 3H-noradrenaline and then superfused with 3H-amine-free medium. They were stimulated either electrically at 2 Hz, or by 60 mM potassium, or by 1 microM tyramine. 2 GABA (1 - 1000 microM) did not change the basal outflow of tritium, but decreased the electrically evoked overflow as well as the contractile response. GABA 1 microM decreased the evoked overflow by 12%, and GABA 1000 microM, by 42%. The effect of GABA was not changed by yohimbine, propranolol, cocaine, corticosterone, or indomethacin. It was not antagonized by picrotoxin or bicuculline methiodide. GABA 100 microM also slightly reduced the potassium-evoked overflow of tritium but did not change the tyramine-evoked overflow. 3 The results show that, in the pulmonary artery of the rabbit, GABA inhibits the release of noradrenaline. Its effect is independent of alpha- and beta-adrenoreceptors and is not mediated by prostaglandins. The effect may be due to activation of presynaptic receptors which appear to differ from conventional GABA receptors inasmuch as they are insensitive to blockade by either picrotoxin or bicuculline.

Animals↗
PubMed1986

Gamma-aminobutyric acid in the genital tract of the rat during the oestrous cycle.

The highest values of gamma-aminobutyric acid (GABA) in the genital tract of the rat at different stages of the oestrous cycle were found in the oviduct (3.5-7 micrograms/mg protein) and the lowest in the ovary (50-100 ng/mg protein). The values for uterus and vagina ranged between 80 and 150 ng/mg protein. GABA (10-30 ng/microliter) was also found in fluid in the ovarian bursa. At 11:00 h, on the day of oestrus, GABA content increased in the ovaries but values in the oviducts were maximal at 11:00 h on the day of pro-oestrus. Variations in GABA content of the vagina were also found. Uterine cervix or uterine horn showed no changes during the oestrous cycle. The GABA content was not uniform throughout the oviduct: the highest values were found in the portion next to the ovary. At 10 days after removal of the right oviduct, GABA values in the ovary and ovarian bursa fluid decreased on the operated side. At 1 month after surgery, the values in ovary were normal but the values in ovarian bursa fluid were still low, suggesting that the source of ovarian GABA was not the oviduct. The variations observed in the present paper suggest an involvement of GABA in reproductive physiology.

Animals↗
PubMed1987

An antinociceptive profile of kojic amine: an analogue of gamma-aminobutyric acid (GABA).

Kojic amine [2-(aminomethyl)-5-hydroxy-4H-pyran-4-one], an analogue of gamma-aminobutyric acid (GABA), produced dose-related, but short-lived, antinociceptive activity in the 48 degrees C [ED50 = 9.2 (8.2-10.3) mg/kg i.p.] and 55 degrees C [ED50 = 13.8 (12.2-15.7) mg/kg i.p.] hot-plate tests in the mouse. The antinociceptive activity of kojic amine at 48 degrees C was found to be insensitive to bicuculline (1.0 mg/kg i.p.) and picrotoxin (0.5 mg/kg i.p.). At this temperature, antinociception was distinctly separate from the impairment of motor function (measured by a rotorod assay) and was not significantly affected by prior treatment with the cholinergic antagonist, atropine sulfate (10.0 mg/kg i.p.). However, at 55 degrees C, the antinociceptive effect of a large dose (20 mg/kg i.p.) of kojic amine was significantly attenuated by similar pretreatment with atropine sulfate, but not by the peripheral cholinergic antagonist, atropine methylnitrate (10.0 mg/kg i.p.). Kojic amine exhibited no significant interaction with haloperidol (0.5 mg/kg i.p.) at this temperature. In animals made tolerant to morphine, THIP or baclofen, there was analgesic cross-tolerance between kojic amine, morphine and baclofen but not between kojic amine and THIP. It is suggested that kojic amine-induced antinociception is similar to that produced by both THIP and baclofen. Thus, kojic amine represents a unique tool with which to study GABA-ergic antinociceptive processes.

Animals↗
PubMed1996

Effect of diazepam on plasma gamma-aminobutyric acid in sons of alcoholic fathers.

A subgroup of abstinent alcoholics, display low levels of plasma gamma-aminobutyric acid (GABA). Two previous studies of plasma GABA in sons of alcoholic fathers (SOAs) have yielded conflicting results. The aim of the current study was to measure plasma GABA both at baseline and after challenge with diazepam, a GABAA receptor agonist, in a group of SOAs already shown to display decreased eye movement, memory, and sedative effects of diazepam. Twenty-seven SOAs and 23 male control subjects received four logarithmically increasing doses of diazepam or placebo in randomized order on 2 days at least 1 week apart. Plasma GABA was measured at baseline and after the last dose. There were no significant differences between SOAs and controls in baseline plasma GABA levels. In the whole sample, there were significant correlations between baseline plasma GABA and both high novelty-seeking and low-harm avoidance scores on the Tridimensional Personality Questionnaire. Both SOAs and controls displayed decreases in plasma GABA over time on both testing days, but there was no effect of diazepam on plasma GABA and no significant difference between groups in plasma GABA response to diazepam. These results suggest that neither low plasma GABA at baseline nor altered plasma GABA response to diazepam is associated with increased genetic risk for alcoholism.

Adolescent↗
PubMed1993

Zinc selectively inhibits flux through benzodiazepine-insensitive gamma-aminobutyric acid chloride channels in cortical and cerebellar microsacs.

The effects of Zn2+ on the activity of gamma-aminobutyric acid (GABA)A receptor-Cl- ionophore complexes found in adult rat cortex and cerebellum were tested by measuring 36Cl- influx into microsacs. In both preparations, the concentration-response curves were biphasic, with 25% of the cerebellar and 20% of the cortical Cl- flux being blocked by less than 10 microM Zn2+ and 45% of the cerebellar and 50% of the cortical flux being blocked by concentrations of Zn2+ exceeding 10 microM. Zn2+ (100 microM) did not affect basal Cl- flux but inhibited that stimulated by 100 microM GABA in a noncompetitive manner. The ability of 1 microM flunitrazepam to enhance Cl- flux was unaffected by 100 microM Zn2+. These results demonstrate that, in adult rat cerebellum and cortex, there are three populations of GABAA receptors, two that are sensitive to Zn2+ and insensitive to benzodiazepines (BDZ) and the remainder that are the reverse, i.e., insensitive to Zn2+ but fully sensitive to BDZ enhancement. This result is consistent with the idea that Zn2+ blocks only those GABAA receptor-Cl- ionophore complexes that lack a gamma subunit, which is required for modulation by BDZ. The results obtained in this study also show that the proportion of Zn(2+)-sensitive GABA receptors is substantial, suggesting that they play an important role in the functioning of the adult central nervous system.

Animals↗
PubMed1989

Effects of lead salts on the uptake, release, and binding of gamma-aminobutyric acid: the importance of buffer composition.

The effects of lead on the uptake and release of gamma-[3H]aminobutyric acid [( 3H]GABA) from rat brain slices were examined in solutions buffered with Tris-HCl, sodium phosphate, and sodium bicarbonate. Lead acetate (10-250 microM) inhibited uptake and potassium-stimulated release and facilitated spontaneous efflux only in solutions buffered with Tris-HCl. Calcium-independent binding of [3H]GABA was unaffected by lead acetate (1-100 microM) in Tris-citrate buffer but was significantly inhibited by 3 microM lead acetate in Tris-HCl solution. At the rat soleus neuromuscular junction, lead caused a dose-dependent reduction of end-plate potential amplitude at concentrations of 10-100 microM lead acetate in HEPES-buffered solution but had no effect at these concentrations in phosphate-buffered solution. Stability constants of lead complexes indicate that buffers containing carbonate and phosphate are unlikely to contain a significant concentration of Pb2+, as complexing by these anions would reduce the availability of free Pb2+. This study indicates that the choice of buffer is important when investigating the effects of lead on biological systems and that negative findings may result from the use of inappropriate buffers. It also has important clinical implications suggesting that some effects of lead poisoning may result from its ability to affect neurotransmitter systems directly and that local changes in pH and complexing anion concentrations in the CNS may influence its biological availability and, hence, variable biological responses.

Animals↗
PubMed1987

Presence of a gamma-aminobutyric acid (GABA) uptake system on cholinergic terminals of rat hippocampus: evidence for neuronal coexistence of acetylcholine and GABA?

The effect of gamma-aminobutyric acid (GABA) on the basal release of [3H]acetylcholine ([3H]ACh) was investigated using synaptosomes prepared from rat hippocampus and superfused after prelabeling with [3H]choline. Exogenous GABA added to the superfusion medium caused a long-lasting and concentration-dependent enhancement of the basal efflux of [3H]ACh. The effect of GABA was not antagonized by bicuculline or picrotoxin. Muscimol increased slightly but not significantly the release of [3H]ACh, whereas (+/-)-baclofen or (-)-baclofen were ineffective. The effect of GABA was counteracted by SK&F 89976A [N-(4,4-diphenyl-3-butenyl)-nipecotic acid], SK&F 100330A [N-(4,4-diphenyl-3-butenyl)-guvacine] and SK&F 100561 [N-(4,4-diphenyl-3-butenyl)-homo-beta-proline], three novel inhibitors of GABA uptake, but was unaffected by hemicholinium-3 or by beta-alanine. Nipecotic acid, a substrate-inhibitor of the GABA transporter, mimicked GABA and enhanced [3H]ACh release. The results indicate that a GABA transport system is present on cholinergic terminals.

Acetylcholine↗
PubMed2002

Opiate-induced motor stimulation is regulated by gamma-aminobutyric acid type B receptors found in the ventral tegmental area in mice.

Recent studies suggest that gamma-aminobutyric acid type B (GABA(B)) receptors located on dopaminergic cells in the ventral tegmental area (VTA) regulate mesolimbic dopaminergic (A10) activity. In the current study, we identified GABA(B) receptor subtypes in the area of the VTA and examined their role in modulating acute opiate actions. We studied the effects of intra-VTA infusions of the selective GABA(B) agonist baclofen on morphine-induced locomotor stimulation and A10 neuronal activation. Drug treatments were followed by ambulatory activity monitoring for 180 min. Intra-VTA baclofen treatment produced a 70% inhibition of morphine-stimulated locomotor activity. Furthermore, functional activation of A10 neurons was assessed by immunohistochemical staining of c-Fos in the nucleus accumbens (NAc), where A10 neurons terminate. We found that morphine treatment increased the levels of Fos-positive nuclei in the NAc, while intra-VTA baclofen treatment reversed morphine's effects. Finally, GABA(B) receptor subtypes and isoforms were identified in the ventromedial mesencephalon using immunoblotting. We demonstrated the presence of GABA(B)R1a (130 kDa), GABA(B)R1b (100 kDa), and GABA(B)R2 (120 kDa) receptor subtypes in this region. These results suggest that GABA(B) receptor isoforms are found in the VTA and their activation results in the blockade of behavioral effects of opiates via inhibition of dopaminergic neurotransmission.

Animals↗
PubMed1999

Spontaneous and gamma-aminobutyric acid (GABA)-activated GABA(A) receptor channels formed by epsilon subunit-containing isoforms.

A new gamma-aminobutyric acid (GABA)A receptor (GABAR) subunit class, epsilon, has recently been cloned and shown to form functional channels when coexpressed with both alpha and beta subunits. We report that the combination of alpha1beta3epsilon subunit subtypes expressed in L929 cells produced functional chloride ion channels that were both spontaneously active and gated by the application of extracellular GABA. When cells were voltage-clamped at -75 mV in the whole-cell configuration, holding currents of 50 to 300 pA associated with increased noise were consistently recorded. The application of pentobarbital and loreclezole, which increase GABAR currents, increased the holding current, whereas the application of zinc and picrotoxin, which reduce GABAR currents, reduced the holding current in a concentration-dependent manner. Coexpression of alpha1beta3gamma2L, alpha1beta3delta, alpha1epsilon, beta3epsilon, alpha1beta3, or epsilon subtypes did not produce holding currents that were sensitive to picrotoxin (30 microM). Cells expressing alpha1 beta3epsilon subtypes had concentration-dependent GABAR currents that were potentiated by pentobarbital, loreclezole, and lanthanum and inhibited by zinc and furosemide. Spontaneous and GABAR single-channel currents from alpha1beta3epsilon receptors had single-channel conductances of approximately 24 pS. The biophysical properties and the effects of allosteric modulators were similar for spontaneous and evoked GABAR currents, suggesting that a single GABAR isoform was responsible for both currents. These data extend the pharmacological characterization of epsilon-containing GABARs and demonstrate that incorporation of the epsilon subunit permits spontaneous channel gating while preserving the structural information necessary for GABA sensitivity.

Animals↗
PubMed2003

[Effects of pyrethroids on the activity of gamma-aminobutyric acid transferase in rat brain].

OBJECTIVE: To study the effects of pyrethroids on the activity of gamma-aminobutyric acid transferase (GABAT) in rat brain. METHOD: The coupled enzyme ultraviolet spectrophotography was applied to observe the effects of deltamethrin (DM) and permethrin (PM) on the activities of GABAT in rat cerebral cortex, hippocampus, corpus striatum and cerebellum in vitro and in vivo. RESULTS: In vitro, DM and PM had no significant effects on the activities of GABAT in rat cerebral cortex, hippocampus, corpus striatum and cerebellum at the final concentration of 10(-9) - 10(-4) mol/L. When 37.5 mg/kg DM and 600 mg/kg PM were orally administrated to the rats at one time, the activities of GABAT in rat cerebral cortex, hippocampus and cerebellum in the DM group [(2.96 +/- 0.43), (2.13 +/-0.44), (5.12 +/- 1.36) nmol x mg pro(-1) x min(-1), respectively] were lower than those in the control group [(3.43 +/- 0.41), (2.68 +/- 0.47), (6.74 +/- 1.64) nmol x mg pro(-1) x min(-1)] (P < 0.05), and the activities of GABAT in rat cerebral cortex and hippocampus in the PM group [(4.57 +/- 0.30), (4.18 +/- 0.63) nmol.mg pro(-1) x min(-1), respectively] were higher than those in the control group (P < 0.05). When 12.5 mg/kg DM and 200 mg/kg PM were orally administrated to the rats once a day for consecutive five days, the two pesticides had no significant effects on the activities of GABAT in rat cerebral cortex, hippocampus, corpus striatum and cerebellum (P > 0.05). CONCLUSIONS: In vitro, DM and PM had no significant effects on the activity of GABAT in rat brain; in vivo, DM and PM may have different effects on the activity of GABAT in rat brain, which deserve further study.

Animals↗
PubMed1996

Effects of gamma-aminobutyric acid on human sperm motility and hyperactivation.

This study was undertaken to evaluate the effects of gamma-aminobutyric acid (GABA) and GABAergic agonists and antagonists on sperm kinematic parameters and hyperactivation, evaluated by a computer-assisted semen analysis (CASA) system, and intracellular cAMP content in 22 normozoospermic semen samples. Because of the possible interaction of progesterone with the GABAA receptor, we also evaluated the effects of progesterone on these parameters. GABA increased beat cross frequency, curvilinear velocity (VCL), the percentage of spermatozoa moving with an average path velocity > 10 microns/s (active) and hyperactivation, and decreased linearity and straightness. Bicuculline, a GABAA receptor antagonist, antagonized the effects of GABA on all these parameters except the percentage of active spermatozoa. Muscimol, a GABAA receptor agonist, increased VCL, the percentage of active spermatozoa, and hyperactivation by about the same extent as GABA, suggesting the involvement of the GABAA receptor. However, the GABAB receptor also seems to mediate some of the effects of GABA, because baclofen, a selective agonist for this receptor, increased significantly the percentage of active spermatozoa and hyperactivation. The effect of baclofen on this latter parameter was, however, less pronounced than that obtained with GABA or muscimol. Progesterone had the same effects as GABA on sperm kinematic parameters and hyperactivation and the simultaneous presence of both compounds was not more effective than each single one. GABA and progesterone did not have any effect on intracellular cAMP content. In conclusion, GABA modulated sperm kinematic parameters and increased hyperactivation. These effects have the same magnitude of those produced by progesterone and seem to be mediated mainly by the GABAA receptor. We speculate that GABA may be a physiological regulator of sperm function.

Baclofen↗
PubMed1998

Maintenance of recombinant type A gamma-aminobutyric acid receptor function: role of protein tyrosine phosphorylation and calcineurin.

In the present study, rundown of gamma-aminobutyric acid (GABA)-activated Cl- channels was studied in recombinant GABAA receptors stably expressed in human embryonic kidney cells (HEK 293), with conventional whole-cell and amphotericin B-perforated patch recording. When [ATP]i was lowered to 1 mM and resting [Ca++]i was buffered to a relatively high level, the response of alpha 3 beta 2 gamma 2 GABAA receptors to relatively low [GABA] (up to 50 microM) did not show rundown in the whole-cell configuration. However, high [GABA] (greater than 200 microM) induced significant rundown, which was observed by decreases in both the maximum GABA-induced current and GABA EC50. Rundown was prevented completely with a solution containing 4 mM Mg(++)-ATP and low resting [Ca++]i, or during perforated patch recording. The magnitude of rundown was comparable in alpha 1 beta 2 gamma 2 and beta 2 gamma 2 receptors. Neither stimulation nor inhibition of protein kinase A or protein kinase C had a significant effect on rundown. However, sodium metavanadate, an inhibitor of protein tyrosine phosphatase, significantly reduced rundown. In addition, inhibition of protein tyrosine kinase activity by either genistein or lavendustin A induced rundown of the GABA response. Inhibition of the Ca++/calmodulin-dependent phosphatase calcineurin with fenvalerate also prevented rundown of the response to GABA. Our results demonstrate that rundown of GABAA receptor function is concentration-dependent, due to depletion of ATP and/or unbuffered [Ca++]i, and does not depend on the presence or subtype of the alpha subunit. We propose that protein phosphorylation at a tyrosine kinase-dependent site, and a distinct unidentified site, which is dephosphorylated by calcineurin, maintains the function of GABAA receptors.

Adenosine Triphosphate↗
PubMed1986

Nipecotic acid, an uptake blocker, prevents fading of the gamma-aminobutyric acid effect.

In rats under urethane, iontophoretic applications of GABA (30-60 nA) in the str. pyramidale of CA1, showed a rapidly fading inhibitory effect. By contrast, GABA had a well-maintained inhibitory effect in str. radiatum. During iontophoresis of nipecotic acid (30-85 nA) identical applications of GABA in str. pyramidale caused a more prominent depression without fading, which suggests that removal of GABA, by uptake, can at least in part account for 'fading'. Nipecotic acid also prolonged the paired-pulse inhibition, presumably by prolonging the duration of inhibitory postsynaptic potentials.

Animals↗
PubMed1996

Homomeric beta 1 gamma-aminobutyric acid A receptor-ion channels: evaluation of pharmacological and physiological properties.

The ubiquitous distribution of gamma-aminobutyric acid A (GABAA) receptor beta subunits throughout the central nervous system is in accord with a vital role in receptor structure and function. Homomeric beta subunits have been reported to be either GABA-gated or capable of forming anion-selective channels that lacked GABA-gating properties. With electrophysiological recording techniques, we examined the properties of the murine Beta 1 subunit, addressed whether the homomeric receptor is expressed independently from the host cell's genome, and investigated whether these channels can open spontaneously. Murine beta 1 subunits, expressed in Xenopus oocytes or A293 cells, were unaffected by GABA or bicuculline; however, the resting membrane conductances were reduced by picrotoxin, zinc, or penicillin-G. In comparison, the expression of bovine beta1 subunits formed GABA-gated C1- channels. For murine beta 1 subunits, both pentobarbitone and propofol increased the membrane conductance, although the benzodiazepine ligands flurazepam, flumazenil, and methyl-6,7-dimethoxy-4 ethyl-beta-carboline-3-carboxylate were inactive. Oocytes injected with murine beta 1 cRNA in the presence of actinomycin D (to block host cell DNA transcription) expressed beta1 channels that were indistinguishable from those derived from previous cDNA injections in cells capable of normal transcription. Single-channel recording from murin beta 1 cDNA-injected oocytes revealed spontaneously opening channels with a main state conductance of 18 pS. Picrotoxin inhibited the channel openings by reducing the probability of opening. We concluded that murine beta 1 subunits can form functional ion channels that are not gated by GABA but can be closed by some noncompetitive GABA antagonists. Interestingly, previous observations of spontaneously opening ion channels with properties similar to those found for the murine beta 1 receptor suggest that a limited expression of homomeric beta subunit-ion channels may exist in vivo.

Animals↗