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R A North

Publications and source records attributed to R A North.

At least 163 records · Page 9Linked to original sources
PubMed1989

Expression of a cloned rat brain potassium channel in Xenopus oocytes.

Potassium channels are ubiquitous membrane proteins with essential roles in nervous tissue, but little is known about the relation between their function and their molecular structure. A complementary DNA library was made from rat hippocampus, and a complementary DNA clone (RBK-1) was isolated. The predicted sequence of the 495-amino acid protein is homologous to potassium channel proteins encoded by the Shaker locus of Drosophila and differs by only three amino acids from the expected product of a mouse clone MBK-1. Messenger RNA transcribed from RBK-1 in vitro directed the expression of potassium channels when it was injected into Xenopus oocytes. The potassium current through the expressed channels resembles both the transient (or A) and the delayed rectifier currents reported in mammalian neurons and is sensitive to both 4-aminopyridine and tetraethylammonium.

4-Aminopyridine↗
PubMed1989

Effects of cisapride on cholinergic neurotransmission and propulsive motility in the guinea pig ileum.

The actions of cisapride on electrical behavior of single myenteric neurons and on the propulsive activity of segments of ileum were studied in vitro. Cisapride (10-300 nM) did not affect the membrane potential, resting properties, or active properties of S neurons. The amplitude of fast nicotinic excitatory postsynaptic potentials recorded from S cells was increased by cisapride in the concentration range of 10 nM to 1 microM. Higher cisapride concentrations (3-10 microM) reduced the amplitude of fast excitatory postsynaptic potentials. Potentiation of fast excitatory postsynaptic potentials by cisapride was antagonized by ICS 205-930 (1 microM) but was unaffected by GR 38032F (1 microM), both compounds being 5-HT3-receptor antagonists. Cisapride did not modify the electrical behavior of AH neurons except at the highest concentrations (3-10 microM), which caused hyperpolarization of some neurons. The propulsive efficiency (i.e., number of peristalses and total amount of fluid ejected per unit of time) of isolated segments of ileum was enhanced by cisapride (100 nM to 3 microM). Higher cisapride concentrations (6 or 10 microM) had a depressant action on propulsive activity. The stimulatory effect of cisapride on propulsion was not antagonized by ICS 205-930 (300 nM or 1 microM). These data indicate that cisapride facilitates cholinergic transmission in the myenteric plexus of guinea pig ileum and that this effect may be at least partially responsible for the increased propulsive efficiency observed in ileal segments.

Acetylcholine↗
PubMed1989

Single potassium channels opened by opioids in rat locus ceruleus neurons.

Currents through single-ion channels were recorded in the cell-attached configuration from locus ceruleus neurons enzymatically dissociated from newborn rats. When the selective mu opioid receptor agonist Tyr-D-Ala-Gly-MePhe-Gly-ol was in the patch-clamp electrode, unitary inward currents were observed with conductance of approximately 45 pS (measured at zero pipette potential, with 150 mM potassium in the recording electrode). Long silences, lasting many seconds to minutes, separated periods of activity of similar durations. Within such activity periods the distribution of closed times of the channels was best fitted by the sum of two exponential functions (time constants approximately 1 and 30 ms), and the durations of channel openings were fit by a single exponential function; mean open time increased from 2 to 120 ms as agonist concentration increased. Channel activity was not seen when high concentrations of opioids were applied to the neuron outside the patch-clamp recording electrode, indicating intimate coupling between receptor and potassium channel. Unitary currents with similar properties were also seen when pipettes contained alpha 2 adrenoceptor agonists or somatostatin. Taken with previous findings, the results indicate that mu opioid receptors, alpha 2 adrenoceptors, and somatostatin receptors can couple directly to membrane potassium channels through the local intermediary action of a GTP binding protein.

Action Potentials↗
PubMed1989

Muscarinic agonists and potassium currents in guinea-pig myenteric neurones.

1. Intracellular electrophysiological recordings were obtained from single neurones of the guinea-pig myenteric plexus in vitro. Using single electrode voltage clamp techniques, four distinct potassium currents were described and the effects of muscarinic agonists on these currents were studied. 2. A calcium-dependent potassium current (gKCa) was present in AH neurones at rest, and was much increased following a brief depolarization (50 ms, to 0 mV). Muscarinic agonists reduced both the resting current and the current evoked by depolarization. Pirenzepine competitively antagonized the suppression by muscarine of the calcium-dependent potassium current (or after-hyperpolarization) following an action potential. The dissociation equilibrium constant for pirenzepine was about 10 nM. 3. The conductance of AH neurones increased two to three fold when they were hyperpolarized negative to -90 mV. This inward rectification was blocked by extracellular caesium (2 mM) or rubidium (2 mM), but not by tetraethylammonium (TEA, 40 mM), 4-aminopyridine (100 microM) or cobalt (2 mM). The inward rectification was unaffected by muscarinic agonists. 4. When AH neurones were depolarized from very negative holding potentials (less than -80 mV) a brief outward current was recorded with a duration of about 200 ms. This transient or A current was completely blocked by 4-aminopyridine (100 microM) but was not affected by tetrodotoxin (300 nM), TEA (40 mM) or cobalt (2 mM). Muscarinic agonists did not affect the A current. 5. In S neurones, and in AH neurones in calcium-free solutions, the potassium conductance (in TEA and caesium) behaved according to constant field assumptions. This background conductance was suppressed by muscarinic agonists. 6. It is concluded that the depolarization by muscarinic agonists of myenteric AH neurones is due to a suppression of both a calcium-dependent potassium conductance and a background potassium conductance. Muscarinic depolarization of S neurones results only from suppression of the background potassium conductance. Effects on both conductances result from M1-receptor activation. Inward rectifying and transient outward (A) potassium currents are unaffected.

Animals↗
PubMed1989

Nicotinic excitation of rat ventral tegmental neurones in vitro studied by intracellular recording.

1. Intracellular recordings were made from presumed dopamine-containing neurones in the ventral tegmental area (VTA) in rat brain slices. 2. Nicotine (10-100 microM) and acetylcholine (ACh) depolarized the neurones. The depolarization caused by ACh was typically biphasic; both components were increased by neostigmine (0.1-10 microM), but only the slower component was blocked by scopolamine (1-10 microM). 3. The nicotinic action of ACh, studied in the presence of neostigmine and scopolamine, persisted in the presence of tetrodotoxin (1 microM) and cobalt (2-5 mM). 4. ACh or carbachol (30 microM) caused inward currents in neurones voltage-clamped near the resting potential. These currents reversed polarity at around -4 mV, were blocked by hexamethonium (1-100 microM) in a voltage-dependent manner, and showed desensitization with prolonged or repeated agonist applications. 5. Depolarizations caused by ACh and carbachol were reduced in slices pretreated with kappa-bungarotoxin, but were not changed by alpha-bungarotoxin. 6. These responses to ACh and nicotine resemble those previously described on autonomic ganglion cells. The direct action on VTA neurones may contribute to the positive reinforcement associated with nicotine consumption.

Acetylcholine↗
PubMed1989

5-Hydroxytryptamine acts at 5-HT2 receptors to decrease potassium conductance in rat nucleus accumbens neurones.

1. Intracellular recordings were made from neurones in the nucleus accumbens in slices from the rat brain maintained in vitro. 2. 5-Hydroxytryptamine (5-HT.1-100 microM) depolarized 170 of 203 (84%) neurones and caused them to discharge action potentials. The depolarization was associated with an increase in the input resistance, and was reversed in polarity by conditioning hyperpolarization; this reversal potential was linearly related to the logarithm of the extracellular potassium concentration. 3. Application of 5-HT to neurones voltage-clamped near their resting potential (typically about -80 mV) caused an inward current and a decrease in the slope conductance. The current caused by 5-HT reversed polarity at the potassium equilibrium potential. Analysis with an equivalent circuit model of the neurone at steady state indicated that 5-HT selectively reduced the inward rectifier potassium conductance. 4. The depolarization caused by 5-HT persisted in tetrodotoxin (1 microM). It was reduced but not abolished by a solution that contained lower levels of calcium (0.24 instead of 2.4 mM), higher levels of magnesium (5 instead of 1.2 mM), and cobalt (2 mM). 5. The depolarization caused by 5-HT was competitively antagonized by the 5-HT2 antagonists ketanserin and mianserin with dissociation equilibrium constants of 3 and 45 nM respectively: spiperone (300 nM) also blocked the action of 5-HT. The depolarization was not mimicked or blocked by a number of other agonists and antagonists selective for the 5-HT1 and 5-HT3 receptor types.

Animals↗
PubMed1989

Inward rectification in rat nucleus accumbens neurons.

1. Intracellular recordings were made from neurons in slices cut from the rat nucleus accumbens septi. Membrane currents were measured with a single-electrode voltage-clamp amplifier in the potential range -50 to -140 mV. 2. In control conditions (2.5 mM potassium), the resting membrane potential of the neurons was -83.4 +/- 1.1 (SE) mV (n = 157). Steady state membrane conductance was voltage dependent, being 34.8 +/- 1.7 nS (n = 25) at -100 mV and 8.0 +/- 0.7 nS (n = 25) at -60 mV. 3. Barium (1 microM) markedly reduced the inward rectification and caused a small inward current (40.6 +/- 8.7 pA, n = 8) at the resting potential. These effects became larger with higher barium concentrations, and, in 100 microM barium, the current-voltage relation was straight. 4. The block of the inward current by barium (at -130 mV) occurred with an exponential time course; the time constant was approximately 1 s at 1 microM barium and less than 90 ms with 100 microM. Strontium had effects similar to those of barium, but 1000-fold higher concentrations were required. Cesium chloride (2 mM) and rubidium chloride (2 mM) also blocked the inward rectification; their action reached steady state within 50 ms. 5. It is concluded that the nucleus accumbens neurons have a potassium conductance with many features of a typical inward rectifier and that this contributes to the potassium conductance at the resting potential.

Animals↗
PubMed1989

1,3-Di(2-tolyl)guanidine blocks nicotinic response in guinea pig myenteric neurons.

Ditolylguanidine (DTG) is a ligand which binds with high affinity to neuronal sigma receptors. Activation of sigma receptors inhibits the release of acetylcholine (ACh) from guinea pig ileum myenteric plexus preparations. A study was therefore undertaken to investigate the action of sigma receptor ligands on single neurons. Nicotinic responses to locally applied ACh onto single neurons of the guinea pig ileum myenteric plexus were studied using intracellular recording techniques. DTG and (+)-SKF10047 (N-allylnormetazocine) produced a concentration-dependent suppression of the depolarization of enteric neurons evoked by ionophoresis of ACh. The EC50 values for DTG and (+)-SKF10047 were 4.7 and 3.8 microM, respectively, and were similar to that for hexamethonium (3.2 microM). The inhibition of the ACh-depolarization was not mediated at sigma receptors because (-)SKF10047 and Bridge-DPG (2-imino-1,3H-dibenzo[d,f]-[1,3]-diazepine), which are inactive at sigma receptors, were as potent as DTG and (+)-SKF10047. DTG and hexamethonium (each at 1 microM) were more effective blockers of ACh-induced inward currents at a holding potential of -100 mV than at -40 mV. This voltage dependence is consistent with a channel blocking mechanism. DTG (10 microM) did not affect the depolarization (mediated by 5-HT3 receptors) induced by pressure application of 5-HT onto single neurons. DTG and Bridge-DPG inhibited contractures of the longitudinal muscle-myenteric plexus preparation elicited by dimethylphenylpiperazinium noncompetitively (EC50 values were 8.0 and 12.3 microM, respectively) whereas DTG but not Bridge-DPG inhibited 5-HT-induced contractions of the longitudinal muscle-myenteric plexus noncompetitively.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Primary glomerulonephritis and pregnancy.

Three hundred and ninety-five pregnancies undertaken by 238 women with primary glomerulonephritis between 1962 and 1987 were analysed to record fetal and maternal outcome and identify risk factors for a poor outcome. Of 398 fetuses, 26 per cent were lost (including therapeutic abortions), 24 per cent surviving infants were premature (less than or equal to 36 weeks gestation) and 51 per cent were term. Excluding therapeutic abortions, 20 per cent of fetuses were lost, 15 per cent after 20 weeks gestation. Fifteen per cent of 237 fetuses whose birth weight was recorded were small for gestational age: Deterioration in maternal renal function was seen in 15 per cent of pregnancies and in 5 per cent of women failed to resolve post partum. Only four women had impaired renal function recorded in the first-trimester and two of these were known to have renal impairment before pregnancy. Hypertension was recorded in 52 per cent of pregnancies, developed early (less than or equal to 32 weeks gestation) in 26 per cent and was severe in 18 per cent. Treated hypertension pre-dated 12 per cent of pregnancies and in 7 per cent (included in the overall incidence of hypertension) exacerbation occurred during pregnancy despite continued antihypertensive medication. Forty-four women (18 per cent) who developed de novo hypertension in pregnancy had permanent hypertension postpartum. Increased proteinuria was recorded in 59 per cent of pregnancies and was irreversible in 15 per cent of women. Comparison of pregnancies which occurred before or after renal biopsy revealed a significantly higher fetal loss rate after 20 weeks gestation in those pregnancies undertaken before the diagnosis of renal disease, and a significantly higher incidence of hypertension and increased proteinuria. Impaired renal function, early or severe hypertension or nephrotic range proteinuria was significantly associated with increased fetal loss, prematurity and fewer full-term infants. There was no significant difference in fetal outcome or maternal complications in pregnancy in patients with treated hypertension before pregnancy and those who were normotensive in the first-trimester. The highest incidence of fetal and maternal complications occurred in patients with primary focal and segmental hyalinosis and sclerosis and the lowest in non-IgA diffuse mesangial proliferative glomerulonephritis. The presence of severe vessel lesions on renal biopsy was associated with a significantly higher total fetal loss and fetal loss after 20 weeks gestation.

Female↗
PubMed1989

Two cell types in rat substantia nigra zona compacta distinguished by membrane properties and the actions of dopamine and opioids.

Intracellular recordings were made from 475 rat substantia nigra zona compacta neurons in vitro. The region from which recordings were made was rich in catecholamine fluorescence. Two groups of neuron, termed principal neurons (95% of the total) and secondary neurons (5% of the total) were clearly distinguishable according to one or more of the following 4 electrophysiological properties. Secondary neurons (23 cells) (1) fired spontaneous action potentials at frequencies greater than 10 Hz, or were quiescent (30%); (2) had action potentials less than 1 msec in duration; (3) did not show time-dependent inward rectification with step hyperpolarization; and (4) had slope conductances of about 4 nS (between -75 and -90 mV). In contrast, principal neurons (1) fired spontaneous action potentials in the range 1-8 Hz, or were quiescent (33%); (2) had action potentials greater than 1 msec in duration; (3) showed pronounced time-dependent inward rectification; and (4) had steady-state membrane slope conductances of around 22 nS (between -75 and -90 mV). Secondary cells were not affected by dopamine but were hyperpolarized by baclofen, GABA, and the mu opioid receptor agonist Tyr-D-Ala-Gly-MePhe-Gly-ol (DAGO). On the other hand, dopamine and baclofen inhibited firing and/or hyperpolarized all principal cells tested, but mu or delta opioid receptor agonists had no effect. The properties of these 2 cell types broadly correspond with those described by electrophysiological studies in vivo, in which case the majority, or principal, cells are believed to be dopaminergic.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗
PubMed1989

Electrical coupling synchronizes subthreshold activity in locus coeruleus neurons in vitro from neonatal rats.

Locus coeruleus neurons in brain slices prepared from neonatal rats have rhythmic oscillations in membrane potential at frequencies ranging from 0.3 to 3 Hz. Recordings from pairs of neurons separated by 50-300 microns showed that this oscillatory activity was synchronized at ages less than 24 d. Slices cut from rats 24-27 d old showed rhythmic activity which was only partially synchronous between cell pairs, but full synchrony could be restored by superfusion with tetraethylammonium (2 mM) and/or barium (2 mM). No synchronous rhythmic activity was observed between neurons in slices from rats 40 d old, even in the presence of tetraethylammonium and barium. In those cells in which rhythmic potential oscillations were synchronous, action potentials occurring in one cell were not observed in the second cell. Electrotonic coupling was directly demonstrated between 41% of neurons (12 of 29 pairs) in slices from rats less than 10 d old but not in tissue from older rats (4 pairs). The input resistance of neurons from neonatal rats (less than 15 d old) was about half (81 M omega) that measured under identical conditions from neurons from adult rats (213 M omega). The electrotonic potential in cells from rats less than 15 d old was best fit by a double exponential, whereas that from adults was best fit by a single exponential. The results demonstrate that significant electrical coupling occurs among locus coeruleus neurons from neonatal rats; this appears to decline with age. The coupling serves as a low-pass filter and causes the synchronized occurrence of membrane potential oscillations. Such a rhythmic background activity within the entire nucleus may be important for the widespread trophic role of the noradrenergic neurons during development.

Animals↗
PubMed1988

Mechanism of synaptic inhibition by noradrenaline acting at alpha 2-adrenoceptors.

The actions of agonists at alpha 2-adrenoceptors were investigated on single cells of the submucous plexus of the guinea pig small intestine. Intracellular recordings were made from neurons in vitro, and noradrenaline and other agonists were applied by adding them to the superfusion solution. The actions of noradrenaline released from terminals of sympathetic nerves was also studied by stimulating the nerves and recording the inhibitory postsynaptic current; this current can be mimicked by brief applications of noradrenaline from a pipette tip positioned within 50 micron of the neuron. The alpha 2-adrenoceptor-bound noradrenaline with an apparent dissociation constant of 15 microM, determined by the method of partial irreversible receptor inactivation: clonidine and 5-bromo-6-(2-imidazolin-2-ylamino)-quinoxaline (UK 14304) had dissociation constants of 36 nM and 2.5 microM respectively. Noradrenaline and UK 14304 caused maximal hyperpolarizations, or outward currents; clonidine was a full agonist in only 4 of 35 cells, a partial agonist in 25 cells, and without effect in 4 cells. Clonidine acted as a competitive antagonist of noradrenaline in those cells in which it lacked agonist action; its dissociation equilibrium constant determined by Schild analysis was about 20 nM. The potassium conductance increased by the alpha 2-adrenoceptor agonists, whether they were applied exogenously or released by stimulation of presynaptic nerves, showed marked inward rectification. The neurons showed inward rectification also in the absence of agonist; both types of rectification were eliminated by rubidium (2 mM), barium (3-30 microM) and caesium (2 mM). When the recording electrodes contained the nonhydrolysable derivative of guanosine 5'-triphosphate (GTP), guanosine 5'-O-(3-thiotriphosphate, GTP-gamma-S), the effects of applied alpha 2-adrenoceptor agonists did not reverse when they were washed from the tissue, implying that GTP hydrolysis is necessary for the termination of agonist action. Pretreatment with pertussis toxin abolished the inhibitory synaptic potential (IPSP) and agonist-induced hyperpolarizations. Phorbol 12,13-dibutyrate, forskolin, cholera toxin and sodium fluoride did not affect the responses to alpha 2-adrenoceptor agonists. The synaptic hyperpolarization resulting from sympathetic nerve stimulation, or the hyperpolarization evoked by a brief (3-5 ms) application of noradrenaline, began after a latency of about 30 and 60 ms respectively.(ABSTRACT TRUNCATED AT 400 WORDS)

Algorithms↗
PubMed1988

Drug receptors on single enteric neurons.

There are many substances contained within enteric nerves which excite or inhibit other nerves when these substances are applied to single neurons. The actions of these substances and of drugs which mimic these actions is to open or close membrane ion channels. The effects on membrane potential are dependent on the nature of the ions which pass through the channel and whether the channel is opened or closed. In the enteric nervous system, drugs can act at one of three broad classes of receptors: [1] those which are part of an ion channel complex and which open either cation channels or chloride channels, both of which result in membrane depolarization [2] those which open potassium channels resulting in hyperpolarization or [3] those which close potassium channels resulting in depolarization. Receptors which open potassium channels are coupled to the channel via a G-protein while receptors which close potassium channels are coupled to the channel, in some cases, via a cyclic AMP-dependent system while in other cases another second messenger system is involved.

Animals↗
PubMed1988

Agonists at mu-opioid, M2-muscarinic and GABAB-receptors increase the same potassium conductance in rat lateral parabrachial neurones.

1. Intracellular recordings of membrane potential and current were made from neurones in the lateral parabrachial nucleus in slices of rat brain in vitro. 2. The membrane was hyperpolarized by the opioid peptides Tyr-D-Ala-Gly-MePhe-Gly-ol (DAGOL, 0.01-1 microM) and [Met5]enkephalin (3-30 microM), though not by Tyr-D-Pen-Gly-Phe-D-Pen and U50488. In two experiments, naloxone competitively antagonized the effects of DAGOL and [Met]enkephalin with equilibrium dissociation constants of 0.8 and 3.2 nM, respectively. 3. Baclofen (0.3-30 microM) also hyperpolarized the neurones; this action was unaffected by naloxone. 4. DAGOL, [Met5]enkephalin and baclofen caused outward currents at the resting potential. These currents reversed polarity at a membrane potential which changed with the logarithm of the extracellular potassium concentration. 5. Muscarine has been shown previously to increase the potassium conductance by an action at M2-receptors: the potassium currents induced by maximal concentrations of muscarine, baclofen and [Met5]enkephalin were non-additive, indicating that these agonists opened the same population of potassium channels. 6. Noradrenaline, UK14304, carboxamidotryptamine, dopamine, adenosine and somatostatin had little or no effect on membrane potential. 7. It is concluded that rat lateral parabrachial neurones express mu-opioid, gamma-aminobutyric acidB (GABAB), and M2-muscarinic receptors: activation of any of these receptors increases the potassium conductance of the membrane and inhibits the neurones through hyperpolarization.

Animals↗
PubMed1988

On the potassium conductance increase activated by GABAB and dopamine D2 receptors in rat substantia nigra neurones.

1. Intracellular recordings were made from 193 substantia nigra zona compacta neurones in slices of rat mesencephalon. All cells were hyperpolarized by baclofen; this was accompanied by a fall in input resistance. Cells voltage clamped at -60 mV showed an outward current associated with a conductance increase in response to baclofen. The baclofen effects were concentration dependent (effective range 0.3-30 microM); the concentration producing half the maximal effect was 1.5 microM. (-)-Baclofen was 300-700 times more potent than (+)-baclofen. 2. The potential change or membrane current caused by baclofen reversed polarity at -108.8 +/- 1.1 mV (n = 10) when the potassium ion concentration was 2.5 mM, -96.0 +/- 2.8 mV (n = 3) in 4.5 mM-potassium and -76.6 +/- 1.7 mV (n = 5) in 10.5 mM-potassium. The relationship between reversal potential and potassium concentration conformed to the Nernst equation. 3. Dopamine was also applied to 119 of these neurones; all exhibited either a hyperpolarization or an outward current. 4. Baclofen and dopamine outward currents were reduced reversibly by barium (100-300 microM) and tetraethylammonium (10 mM). Superfusion for 5-10 min with solutions presumed to block calcium currents reduced, but did not abolish, responses to baclofen. The effect of baclofen persisted in tetrodotoxin (1 microM). 5. Superfusion of gamma-aminobutyric acid (GABA, 0.3-3 mM) caused either membrane depolarization or hyperpolarization, accompanied by a fall in input resistance. The depolarization was mimicked by muscimol (10 microM) and blocked by bicuculline methiodide (10-100 microM); the hyperpolarization was resistant to bicuculline. Nipecotic acid (500 microM) enhanced the effect of GABA, but was without effect upon the actions of muscimol and baclofen. 6. The effect of dopamine was enhanced by cocaine (10 microM) and antagonized by (-)-sulpiride (0.1-1 microM), whereas the actions of baclofen were unaffected by cocaine or (-)-sulpiride. The maximum outward current produced by dopamine was approximately half that produced by baclofen. 7. Outward currents produced by dopamine were reversibly occluded by maximal outward currents caused by baclofen. 8. Baclofen and dopamine hyperpolarizations were unaffected by intracerebroventricular injection of animals with pertussis toxin. 9. Cells impaled with electrodes containing guanosine 5'-O-(3-thiotriphosphate) (1 mM) were hyperpolarized by both baclofen and dopamine, but the membrane potential did not fully return to its original level when agonist application was discontinued. 10. It is concluded that activation of both dopamine D2 and GABAB receptors may increase the same potassium conductance.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗
PubMed1988

Synaptic potentials in rat locus coeruleus neurones.

1. Intracellular recordings were made from locus coeruleus neurones in a slice of tissue cut from the rat pons. A depolarizing postsynaptic potential (PSP) followed electrical stimulation of the slice surface; the latency was 1-3 ms and the duration was 50-200 ms. 2. The reversal potential of the PSP (estimated by extrapolation from potentials between -60 and -90 mV) was -27 mV when the recording electrodes contained potassium chloride, and -36 mV when electrodes contained potassium acetate or methylsulphate. 3. Kynurenic acid depressed the PSP amplitude by up to 60%. The residual PSP reversed polarity at -50 mV (extrapolated, potassium chloride in electrodes) or -70 mV (observed, potassium methylsulphate in electrodes): it was blocked by bicuculline (10 microM). 4. Exogenously applied gamma-aminobutyric acid (GABA) depolarized cells when the recording electrode contained potassium chloride (reversal potential was -45 mV) and hyperpolarized cells when the recording electrode contained potassium methylsulphate (reversal potential was -70 mV). 5. In the presence of bicuculline, the residual PSP was blocked by kynurenic acid, whereas DL-2-amino-5-phosphonovaleric acid (2-APV) reduced its amplitude to 80% of control. 6. Exogenously applied glutamate, quisqualate and N-methyl-D-aspartate (NMDA) all caused a membrane depolarization (or an inward current under voltage clamp) which reversed polarity at about 0 mV. These effects were blocked by kynurenic acid (500 microM); 2-APV (50 microM) selectively blocked the effect of NMDA. 7. The results indicate that the PSP evoked by focal stimulation within the nucleus locus coeruleus results from an excitatory amino acid acting predominantly at non-NMDA receptors, and from GABA acting at GABAA receptors.

2-Amino-5-phosphonovalerate↗
PubMed1988

Differential localization of 5-HT1 receptors on myenteric and submucosal neurons.

Intracellular recordings were made from guinea pig enteric neurons, and the effects of 5-hydroxytryptamine (5-HT) and the 5-HT1 selective agonists 5-carboxyamidotryptamine (5-CT) and 8-hydroxy-2-(n-dipropylamino)tetralin (DPAT) were studied on membrane potential and synaptic potentials. Most myenteric AH neurons were hyperpolarized when these agonists were applied by superfusion; this hyperpolarization was due to an increase in potassium conductance. Membrane hyperpolarizations to 5-HT, 5-CT, or DPAT were never observed in submucous neurons. Fast nicotinic excitatory postsynaptic potentials (EPSPs) and slow EPSPs recorded from S neurons in the myenteric plexus were suppressed by 5-HT, 5-CT, and DPAT; slow EPSPs in myenteric AH neurons were also inhibited by these agonists. Fast and slow EPSPs recorded from submucous S neurons were not affected by 5-CT or DPAT. However, slow EPSPs recorded from submucous AH neurons were readily blocked by 5-CT and DPAT. The results indicate that 5-HT1 receptors are located on the cell bodies of myenteric but not submucosal neurons. The nerve terminals that release the mediator or mediators of fast and slow synaptic potentials in myenteric neurons also have 5-HT1 receptors and presumably arise from other myenteric neurons; the nerve terminals responsible for the slow EPSP to AH neurons seem to be the only elements of the submucous plexus that express 5-HT1 receptors.

8-Hydroxy-2-(di-n-propylamino)tetralin↗