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J B Furness

Publications and source records attributed to J B Furness.

At least 19 recordsLinked to original sources
PubMed2006

Localization of P2X2 and P2X3 receptors in rat trigeminal ganglion neurons.

Purine receptors have been implicated in central neurotransmission from nociceptive primary afferent neurons, and ATP-mediated currents in sensory neurons have been shown to be mediated by both P2X3 and P2X2/3 receptors. The aim of the present study was to quantitatively examine the distribution of P2X2 and P2X3 receptors in primary afferent cell bodies in the rat trigeminal ganglion, including those innervating the dura. In order to determine the classes of neurons that express these receptor subtypes, purine receptor immunoreactivity was examined for colocalization with markers of myelinated (neurofilament 200; NF200) or mostly unmyelinated, non-peptidergic fibers (Bandeiraea simplicifolia isolectin B4; IB4). Forty percent of P2X2 and 64% of P2X3 receptor-expressing cells were IB4 positive, and 33% of P2X2 and 31% of P2X3 receptor-expressing cells were NF200 positive. Approximately 40% of cells expressing P2X2 receptors also expressed P2X3 receptors and vice versa. Trigeminal ganglion neurons innervating the dura mater were retrogradely labeled and 52% of these neurons expressed either P2X2 or P2X3 or both receptors. These results are consistent with electrophysiological findings that P2X receptors exist on the central terminals of trigeminal afferent neurons, and provide evidence that afferents supplying the dura express both receptors. In addition, the data suggest specific differences exist in P2X receptor expression between the spinal and trigeminal nociceptive systems.

Animals↗
PubMed2005

A quantitative approach to recording peristaltic activity from segments of rat small intestine in vivo.

We have developed methods that allow correlation of propulsive reflexes of the intestine with measurements of intraluminal pressure, fluid movement and spatio-temporal maps of intestinal wall movements for the first time in vivo. A segment of jejunum was cannulated and set up in a Trendelenburg recording system while remaining connected to the vascular and nerve supply of the anaesthetized rat. The resting intraluminal pressure in intact intestine was 2-4 mmHg. Hydrostatic pressures of 2, 4, 8 and 16 mmHg were imposed. At a baseline pressure of 4 mmHg, propulsive waves generated pressures of 9 +/- 1 mmHg, that progressed oral to anal at 2-5 mm s(-1). Individual propulsive waves propelled 0.8 +/- 0.4 mL of fluid. The frequency of propulsive waves increased with pressure, but peristaltic efficiency (mL per contraction) decreased with pressure increase between 4 and 16 mmHg. Atropine, as a bolus, transiently blocked peristalsis, but caused maintained block when infused. Hexamethonium blocked propulsive contractions. Inhibition of nitrergic transmission converted regular peristalsis to non-propulsive contractions. These studies demonstrate the utility of an adapted Trendelenburg method for quantitative investigation of motility and pharmacology of enteric reflexes in vivo.

Animals↗
PubMed2005

Motor patterns and propulsion in the rat intestine in vivo recorded by spatio-temporal maps.

We have used spatio-temporal maps derived from video images to investigate propagated contractions of the rat small intestine in vivo. The abdomen, including an exteriorized segment of jejunum, was housed in a humid chamber with a viewing window. Video records were converted to spatio-temporal maps of jejunal diameter changes. Intraluminal pressure and fluid outflow were measured. Contractions occupied 3.8 +/- 0.2 cm of intestine and propagated anally at 3.1 +/- 0.2 mm s(-1) when baseline pressure was 4 mmHg. Contractions at any one point lasted 8.7 +/- 0.6 s. Contractions often occurred in clusters; within cluster frequencies were 2.28 +/- 0.04 min(-1). Pressure waves, with amplitudes greater than about 9 mmHg, expelled fluid when the baseline pressure was 4 mmHg. In the presence of L-NAME, circular muscle contractions occurred at a high frequency, but they were not propagated. We conclude that video recording methods give good spatio-temporal resolution of intestinal movement when applied in vivo. They reveal neurally-mediated propulsive contractions, similar to those previously recorded from intestinal segments in vitro. The propagated contractions had speeds of propagation that were slower and frequencies of occurrence that were less than speeds and frequencies of slow waves in the rat small intestine.

Anal Canal↗
PubMed2004

Evidence that a major site of expression of the RHO-GTPASE activating protein, oligophrenin-1, is peripheral myelin.

Oligophrenin-1 is a recently discovered Rho-GTPase activating protein, mutation of which is associated with X-linked mental retardation. Since little is known about the cellular localization of oligophrenin-1 in central and peripheral neurons, we investigated its expression by RT-PCR and immunochemical analysis. Oligophrenin-1 immunoreactivity was found in glial cells forming myelin sheaths in the vagus nerve, sciatic nerve and dorsal roots of guinea-pig, rat and human, in chromaffin cells of the adrenal medulla, and in chromaffin cells associated with sympathetic ganglia. No immunoreactivity was detected in sympathetic neurons, in glial cells surrounding these neurons, in optic nerve or in spinal cord myelin. The full length cDNA sequence was determined from guinea-pig sciatic nerve. The translated amino acid sequence was 99% identical to the published human oligophrenin-1 sequence. Western blotting revealed two protein forms which were expressed to different relative extents in different tissues. A 91 kDa form was predominant in extracts of sciatic nerve whereas a 36 kDa form was relatively more abundant in adrenal medulla and brain. Greater amounts of the full length oligophrenin-1 protein occurred in the sciatic nerve of adult rats, compared with P2 rats, which reflects the development of myelination. The presence of multiple forms does not appear to be due to alternative mRNA splicing since RT-PCR products amplified from a variety of tissues were identical and only a single mRNA transcript of 7.4 kb was identified by Northern analysis. These findings demonstrate that a major site of oligophrenin-1 expression is peripheral myelin.

Amino Acid Sequence↗
PubMed2004

Molecular and functional analysis of hyperpolarisation-activated nucleotide-gated (HCN) channels in the enteric nervous system.

Hyperpolarisation-activated non-specific cation currents (Ih currents) are important for the regulation of cell excitability. These currents are carried by channels of the hyperpolarisation-activated nucleotide-gated (HCN) family, of which there are four known subtypes. In the enteric nervous system (ENS), the Ih current is prominent in AH neurons. We investigated the expression and localization of HCN isoforms in the ENS of mice, rats and guinea-pigs. HCN1, HCN2 and HCN4 were expressed in enteric neurons. Immunoreactivity for HCN1 was observed on neuronal cell membranes of Dogiel type II neurons in rat and mouse. HCN2 channel immunoreactivity occurred in the majority of enteric neurons in the guinea-pig, rat and mouse. Immunoreactivity for HCN4 protein was revealed on the cell membranes of many neurons, including Dogiel type II neurons, in the guinea-pig. HCN4 was expressed by glial cells in guinea-pig. There was no evidence of HCN3 channel protein in any species with either immunohistochemistry or Western analysis. RT-PCR (polymerase chain reaction) using mouse HCN primers revealed mRNA for all four channels in the longitudinal muscle plus myenteric plexus of mouse distal colon. Sequencing confirmed the identity of the mRNA. Quantitative PCR demonstrated that HCN2 was the most highly expressed HCN channel subtype in the myenteric plexus of mouse distal colon. HCN1 and HCN4 were expressed at lower levels. HCN3 subtype mRNA was 0.2% of HCN2. We used intracellular recording to identify neurons having Ih currents and intracellular dye filling to locate the neurons for the immunohistochemical determination of channel expression. AH neurons with Ih currents were HCN2 and HCN4 channel positive. There was no correlation between the magnitude of the Ih and intensity of channel immunoreactivity. Our results indicate that HCN1, 2 and 4 genes and protein are expressed in the ENS. AH/Dogiel type II neurons, which have a prominent Ih, express HCN2 and 4 in guinea-pig and HCN1 and 2 in mouse and rat.

Animals↗
PubMed2004

Suppression of a slow post-spike afterhyperpolarization by calcineurin inhibitors.

A subset of myenteric neurons in the intestine (AH neurons) generate prolonged (>5 s) post-spike afterhyperpolarizations (slow AHPs) that are insensitive to apamin and tetraethylammonium. Generation of slow AHPs depends critically on Ca(2+) entry and intracellular release of Ca(2+) from stores, which then leads to the activation of a K(+) conductance that underlies the slow AHP (g(sAHP)). Slow AHPs are inhibited by stimulation of the cAMP/protein kinase A (PKA) pathway, suggesting that phosphorylation of the K(+)-channels that mediate the g(sAHP) (K(sAHP)-channels) is responsible for suppression of slow AHPs and possibly for the repolarization phase of slow AHPs. In the present study, we investigated the possibility that the rising phase of the slow AHP is mediated by dephosphorylation of K(sAHP)-channels by calcineurin (CaN), a Ca(2+)-calmodulin-dependent protein phosphatase, leading to an increase in g(sAHP) and activation of the associated current I(sAHP). Slow AHPs and I(sAHP) were recorded using conventional recording techniques, and we tested the actions of two inhibitors of CaN, FK506 and cyclosporin A, and also the effect of the CaN autoinhibitory peptide applied intracellularly, on these events. We report here that all three treatments inhibited the slow AHP and I(sAHP) (>70%) without significantly affecting the ability of neurons to fire action potentials. In addition, the slow AHP and I(sAHP) were suppressed by okadaic acid, an inhibitor of protein phosphatases 1 and 2A. Our results indicate that activation of the g(sAHP) that underlies the post-depolarization slow AHPs in AH neurons is mediated by the actions CaN and non-Ca(2+)-dependent phosphatases.

Action Potentials↗
PubMed2004

Effects of the peripherally acting NK receptor antagonist, SB-235375, on intestinal and somatic nociceptive responses and on intestinal motility in anaesthetized rats.

We investigated the effects of the selective NK(3) tachykinin receptor antagonist, SB-235375, on noxious signalling from gut and skin and on intestinal motility in anaesthetized rats. We also measured penetrance into brain and spinal cord. Nociceptive responses in reaction to colorectal distension and skin pinch were assessed by recording the electromyogram (EMG) from the external oblique muscle (a visceromotor response). Motility was measured by recording intraluminal pressure waves during changes in baseline pressure in the jejunum. Colorectal compliance was assessed by measuring luminal pressure change during isovolumic distension. SB-235375 (20 mg kg(-1), by i.v. bolus) reduced the EMG response to colorectal distension by over 90%. The reduction was slow at onset, peaked at about 60 min, and lasted for over 2 h. Responses to noxious skin pinch were unchanged. Amplitudes of propulsive waves in the jejunum were slightly reduced, but their frequency of occurrence was unchanged. SB-235375 decreased colorectal compliance by 5-10%. There was undetectable penetration of i.v. SB-235375 into brain or spinal cord. We conclude that SB-235375 acts peripherally to substantially reduce nociceptive signalling from colorectum without affecting noxious signalling from skin and with little effect on intestinal motility.

Acetates↗
PubMed2004

Intrinsic primary afferent neurones of the digestive tract.

Intrinsic primary afferent neurones of the intestine are specialized neurones that encode information about the state of the intestine by transducing mechanical and chemical stimuli that reflect tension in the gut wall and the chemical nature of its contents. They connect with interneurones and motor neurones in the gut to form the circuits of intrinsic muscle motor, secretomotor and vasomotor reflexes. A large range of ionic currents occur in these neurones. The neurones have voltage-activated inward sodium currents (both tetrodotoxin-sensitive and tetrodotoxin-insensitive) and inward calcium currents. Calcium entering during the action potential activates a slow after hyperpolarizing potassium current that has a profound influence on subsequent action potential firing. They also exhibit a prominent hyperpolarization-activated nonspecific cation current. The excitability of these neurones and sensory transduction are altered when the gut is inflamed. Changed excitability can persist after the inflammatory state has subsided. Intrinsic primary afferent neurones are thus important, both to the normal physiology and to pathophysiology of the small and large intestines.

Action Potentials↗
PubMed2003

Analysis of purinergic and cholinergic fast synaptic transmission to identified myenteric neurons.

Types and projections of neurons that received cholinergic, purinergic and other fast excitatory synaptic inputs in myenteric ganglia of the guinea-pig distal colon were identified using combined electrophysiological recording, application of selective antagonists, marker dye filling via the recording microelectrode, and immunohistochemical characterisation. Fast synaptic inputs were recorded from all major subtypes of uniaxonal neurons including Dogiel type I neurons, filamentous interneurons, circular muscle motor neurons and longitudinal muscle motor neurons. Fast excitatory postsynaptic potentials were completely blocked by the nicotinic receptor antagonists hexamethonium or mecamylamine in 62% of neurons tested and were partially inhibited in the remaining neurons. The P2 purine receptor antagonist, pyridoxal-phosphate-6-azophenyl-2',4'-disulfonic acid, reduced the amplitudes of fast excitatory postsynaptic potentials in 20% of myenteric neurons. The 5-hydroxytryptamine(3) receptor antagonist granisetron reduced the amplitude of fast excitatory postsynaptic potentials in only one of 15 neurons tested. In five of five neurons tested, the combination of a nicotinic antagonist, pyridoxal-phosphate-6-azophenyl-2',4'-disulfonic acid, granisetron and 6-cyano-7-nitroquinoxaline-2,3-dione did not completely block the fast excitatory postsynaptic potentials. Immunohistochemical studies of the neurons that had been identified electrophysiologically and morphologically imply that P2X(2) receptors may mediate fast transmission in some neurons, and that other P2X receptor subtypes may also be involved in fast synaptic transmission to myenteric neurons of the guinea-pig distal colon. Neurons with nicotinic and pyridoxal-phosphate-6-azophenyl-2',4'-disulfonic acid-sensitive fast excitatory postsynaptic potentials were present in both ascending and descending pathways in the distal colon. Thus, neither cholinergic nor mixed cholinergic/purinergic synaptic responses are confined to a particular class of neuron. The results indicate that acetylcholine and ATP are the major fast excitatory neurotransmitters in guinea-pig distal colon myenteric ganglia.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed2003

Analysis of factors that determine the compliance of rat jejunum to distension in vivo.

Distension of the intestine is commonly used to elicit reflex responses at other sites in the gastrointestinal tract, and also to evaluate pain of intestinal origin. The sensory neurones, that initiate the reflexes or pain responses, react to the forces generated in the wall of the intestine. Thus, the responses of the intestine at the site of distension, particularly changes in contractile activity, influence the signals from the gut. In the present work we have analysed the relationship between distension and pressure changes in the jejunum of the rat, in vivo. Isovolumic distension for 5 min caused an initial pressure increase which declined quickly in the first 30 s, and then declined more slowly. Phasic pressure increases were superimposed on the baseline pressure change. Hexamethonium blocked the phasic pressure increases, whereas the initial rapid and subsequent slower pressure decline during distension persisted. Inhibition of nitric oxide synthase (NOS) increased intraluminal pressure and caused increased frequency and irregularity of phasic pressure increases. However, the decline in jejunal pressure during distension was not changed by inhibition of NOS. The pressure decline during isovolumic distension was similar whether saline or paraffin oil were used to distend the intestine, indicating that the decline was not due to increased hydrostatic pressure causing water and electrolyte to cross the mucosal epithelium from the lumen to the intestinal interstitium. Hyoscine had no significant effect on the pressure profile when the intestine was distended. However, when the systemic or the local circulation of the jejunum was infused with nicardipine, the pressure that was achieved during isovolumic distension was less, although the rate of change in pressure during the slow decline was similar. It is concluded that distension evokes phasic pressure increases in the jejunum, that are nerve-mediated, and increases the tension in the wall through a stretch-activated increase in contractile force generated by the circular muscle. The decline in pressure during maintained distension is primarily a consequence of visco-elastic properties of the wall of the intestine.

Animals↗
PubMed2002

Responses of myenteric S neurones to low frequency stimulation of their synaptic inputs.

Previous experiments have shown that prolonged low frequency stimulation of presynaptic inputs causes excitation of AH neurones that considerably outlasts the period of stimulation in the guinea-pig small intestine. The present experiments compare the responses of S neurones (which are motor neurones and interneurones) with responses of AH neurones (intrinsic primary afferent neurones) to low frequency stimulation of synaptic inputs. Neurones in the myenteric plexus of isolated segments of guinea-pig small intestine were recorded from with intracellular microelectrodes. During their impalement, the neurones were filled with a marker dye and they were later processed to reveal their shapes and immunohistochemical properties. One group of neurones, inhibitory motor neurones to the circular muscle, was depolarised by stimulation of synaptic inputs at 1 Hz for 100 s to 4 min. With 4-min trains of stimuli, peak depolarisation was 21+/-2 mV (mean+/-S.E.M.), which was reached at about 110 s. Depolarisation was accompanied by increased excitability; before stimulation, a test intracellular pulse (500 ms) triggered 3 action potentials, at the peak of excitability this reached 16 action potentials. Depolarisation began to decline immediately at the end of stimulation. This contrasts with responses of AH neurones, in which depolarisation persisted after the end of the stimulus (peak depolarisation at 300 s). The excitation and depolarisation of inhibitory motor neurones was blocked by the neurokinin 1 tachykinin receptor antagonist, SR140333 (100 nM), but excitation of AH neurones was not affected. Small or no responses to 1 Hz stimulation were recorded from descending filamentous interneurones, longitudinal muscle motor neurones and excitatory circular muscle motor neurones. In conclusion, this study indicates that sustained slow postsynaptic excitation only occurs in AH neurones, and that one type of S neurones, inhibitory motor neurones to the circular muscle, responds substantially, but not beyond the period of stimulation, to activation of synaptic inputs at 1 Hz. This slow excitatory postsynaptic potential evoked by low frequency stimulation is mediated by tachykinins.

Action Potentials↗
PubMed2002

Action potential afterdepolarization mediated by a Ca2+-activated cation conductance in myenteric AH neurons.

We investigated the nature of afterdepolarizing potentials in AH neurons from the guinea-pig duodenum using whole-cell patch-clamp recordings in intact myenteric ganglia. Afterdepolarizing potentials were minimally activated following action-potential firing under normal conditions, but after application of charybdotoxin (40 nM) or tetraethyl ammonium (TEA; 10-20 mM) to the bathing solution, prominent afterdepolarizing potentials followed action potentials. The whole-cell current underlying afterdepolarizing potentials (I(ADP)) in the presence of TEA (10-20 mM) reversed at -38 mV and was not voltage-dependent. Reduction of NaCl in the bathing (Krebs) solution to 58 mM shifted the reversal potential of the I(ADP) to -58 mV, suggesting that the current underlying the afterdepolarizing potential was carried by a mixture of cations. The relative contributions of Na(+) and K(+) to this current were estimated to be about 1:5. Substitution of external Na(+) with N-methyl D-glucamine blocked the current while replacement of internal Cl(-) with gluconate did not block the I(ADP). The I(ADP) was also inhibited when CsCl-filled patch pipettes were used. The I(ADP) was blocked or substantially decreased in amplitude in the presence of N-type Ca(2+) channel antagonists, omega-conotoxin GVIA and omega-conotoxin MVIIC, respectively, and was eliminated by external Cd(2+), indicating that it was dependent on Ca(2+) entry. The I(ADP) was also inhibited by ryanodine (10-20 microM), indicating that Ca(2+)-induced Ca(2+) release was involved in its activation. Niflumic acid consistently inhibited the I(ADP) with an IC(50) of 63 microM. Using antibodies against the pore-forming subunits of L-, N- and P/Q-type voltage-gated Ca(2+) channels, we have demonstrated that myenteric AH neurons express N- and P/Q, but not L-type voltage-gated Ca(2+) channels. We conclude that the ADP in myenteric AH neurons, in the presence of an L-type Ca(2+)-channel blocker, is generated by the opening of Ca(2+)-activated non-selective cation channels following action potential-mediated Ca(2+) entry mainly through N-type Ca(2+) channels. Ca(2+) release from ryanodine-sensitive stores triggered by Ca(2+) entry contributes significantly to the activation of this current.

Action Potentials↗
PubMed2001

Effects of vagal and splanchnic section on food intake, weight, serum leptin and hypothalamic neuropeptide Y in rat.

Truncal vagotomy can cause reduced food intake and weight loss in humans and laboratory animals. In order to investigate some of the factors that might contribute to this effect, we studied changes in ingestive behaviour, whole body and organ weights, serum leptin and hypothalamic neuropeptide Y in rats with bilateral vagal section, bilateral splanchnic nerve section and combined vagotomy plus splanchnectomy. Pyloromyotomy was combined with vagotomy to lessen effects of vagotomy on gastric emptying. Animals with vagotomy or vagotomy plus splanchnectomy lost weight and decreased their daily food intake relative to animals with splanchnectomy alone, rats with bilateral sham exposure of one or both nerve, or rats with pyloromyotomy alone. Serum leptin and white fat mass, 4 weeks after vagotomy, were about 20% of the values in the sham-operated animals at this time. No effect for splanchnic nerve section alone was observed. Pyloromyotomy caused no reduction in weight or fat mass, but reduced serum leptin. Following vagotomy with or without splanchnic nerve section, neuropeptide Y was elevated in the arcuate nucleus relative to values for the other four groups. Changes in neuropeptide Y were inversely correlated with levels of serum leptin. It is concluded that the effect of vagotomy could be due to the loss of a feeding signal carried by vagal afferent neurons, or to changed humoral signals, for example, increased production of a satiety hormone. However, it cannot be attributed to signals that reduce feeding (for example, gastric distension) reaching the central nervous system via the splanchnic nerves. The changes were sufficient to cause weight loss even though serum leptin was decreased, a change that would be expected to increase food intake.

Adipose Tissue↗
PubMed2001

Relationship between postsynaptic NK(1) receptor distribution and nerve terminals innervating myenteric neurons in the guinea-pig ileum.

The amounts of neurokinin 1 (NK(1)) receptor immunolabelling on the membranes of myenteric cell bodies at appositions with tachykinin-immunoreactive nerve terminals, other nerve terminals, and glial cells were compared at the ultrastructural level using pre-embedding, double-label immunocytochemistry. NK(1) receptor immunoreactivity was revealed using silver-intensified, 1 nm gold, and tachykinin-immunoreactive nerve terminals were revealed using diaminobenzidine. The density of NK(1) receptor immunolabelling (silver particles per length of cell membrane) on the membrane at appositions with tachykinin-immunoreactive nerve terminals was not significantly different from that at appositions with other (nonimmunoreactive) nerve terminals or with glial cells. Synaptic specializations ("active zones") were present at a small proportion of the appositions between NK(1) receptor-immunoreactive cell bodies and tachykinin-immunoreactive or other nerve terminals. The density of NK(1) receptor immunolabelling at synaptic specializations was lower than that at regions of appositions where no synaptic specializations were present. The presence of NK(1) receptor on the cell surface in areas not directly apposed to tachykinin-containing nerve terminals suggests that tachykinins that diffuse away from their site of release may still exert an action via NK(1) receptors. Although NK(1) receptors do not appear to be targetted to particular sites on the surfaces of myenteric nerve cell bodies and proximal dendrites, they are reduced in density at regions of the membrane-forming synaptic specializations.

Animals↗
PubMed2001

Calbindin immunoreactivity of enteric neurons in the guinea-pig ileum.

Previous studies have identified Dogiel type II neurons with cell bodies in the myenteric plexus of guinea-pig ileum to be intrinsic primary afferent neurons. These neurons also have distinctive electrophysiological characteristics (they are AH neurons) and 82-84% are immunoreactive for calbindin. They are the only calbindin-immunoreactive neurons in the plexus. Neurons with analogous shape and electrophysiology are found in submucosal ganglia, but, with antibodies used in previous studies, they lack calbindin immunoreactivity. An antiserum that is more effective in revealing calbindin in the guinea-pig enteric nervous system has been reported recently. In the present work, we found that this antiserum reveals the same population that was previously identified in myenteric ganglia, and does not reveal any further population of myenteric nerve cells. In submucosal ganglia, 9-10% of nerve cells were calbindin immunoreactive with this antiserum. The submucosal neurons with calbindin immunoreactivity were also immunoreactive for choline acetyltransferase, but not for neuropeptide Y (NPY) or vasoactive intestinal peptide (VIP). Small calbindin-immunoreactive neurons (average profile 130 microm2) were calretinin immunoreactive, whereas the large calbindin-immunoreactive neurons (average profile 330 microm2) had tachykinin (substance P) immunoreactivity. Calbindin immunoreactivity was seen in about 50% of the calretinin neurons and 40% of the tachykinin-immunoreactive submucosal neurons. It is concluded that, in the guinea-pig ileum, only one class of myenteric neuron, the AH/Dogiel type II neuron, is calbindin immunoreactive, but, in the submucosal ganglia, calbindin immunoreactivity occurs in cholinergic, calretinin-immunoreactive, secretomotor/vasodilator neurons and AH/Dogiel type II neurons.

Animals↗
PubMed2001

Electrophysiological characteristics distinguish three classes of neuron in submucosal ganglia of the guinea-pig distal colon.

Intracellular recordings were made from neurons in the submucosal ganglia of the guinea-pig distal colon. The recording electrode contained the intracellular marker biocytin, which was injected into neurons so that their electrophysiological characteristics could be correlated with their shape. Correlations of electrophysiology and shape have not been reported previously for neurons in this region. Three types of neuron were identified on electrophysiological grounds. Neurons of the first type (S neurons) had tetrodotoxin-sensitive soma action potentials, and received fast and slow excitatory synaptic inputs. They had uniaxonal morphologies and may function as secretomotor or possibly vasomotor neurons. The second type (AH neurons) received only slow synaptic input, while the soma action potential had tetrodotoxin-sensitive and -insensitive components with a shoulder on the falling phase and a long-lasting afterhyperpolarisation of the membrane potential following a single action potential. Neurons of this type had multipolar morphologies and provided dense innervation of adjacent submucosal ganglia. These neurons are similar to the submucosal intrinsic primary afferent neurons of the guinea-pig small intestine. The final type of neuron [the low-threshold (LT) neuron] had electrophysiological characteristics that set it apart from those described previously within enteric plexuses. They expressed tetrodotoxin-insensitive voltage-gated soma currents, did not have long-lasting afterhyperpolarisations and received only slow synaptic input. In addition, these neurons were very excitable: they had large input resistances and low thresholds for action potential discharge, and often fired action potentials in the absence of stimulation. Neurons with these characteristics were uniaxonal and thus are likely to be secretomotor or possibly vasomotor neurons. This study has shown that submucosal neurons of the distal colon fall into three distinct types, which can be distinguished by a combination of electrophysiological and morphological criteria.

Action Potentials↗
PubMed2001

Comparison of the effects of neurokinin-3 receptor blockade on two forms of slow synaptic transmission in myenteric AH neurons.

AH neurons are intrinsic sensory neurons of the intestine that exhibit two types of slow synaptic event: slow excitatory postsynaptic potentials which increase their excitability for about 2-4 min, and sustained slow postsynaptic excitation which can persist for several hours, and may be involved in long-term changes in the sensitivity of the intestine to sensory stimuli. The effects of the neurokinin-3 tachykinin receptor antagonist, SR142801, on these two types of synaptic event in AH neurons of the myenteric ganglia of guinea-pig small intestine were compared. Slow excitatory postsynaptic potentials were evoked by stimulation of synaptic inputs at 10-20 Hz for 1s, and sustained slow postsynaptic excitation was evoked by stimulation of inputs at 1Hz for 4 min. SR142801 (1microM) reduced the amplitude of the slow excitatory postsynaptic potential to 26% of control, and also reduced the increase in input resistance and the extent of anode break excitation associated with the slow excitatory postsynaptic potential. In contrast, SR142801 did not reduce the increase in excitability, the increase in input resistance or the depolarisation that occur during the sustained slow postsynaptic excitation. SR142801 did not change the resting membrane potential or the resting input resistance. We conclude that tachykinins, acting through neurokinin-3 receptors, are involved in the generation of the slow excitatory postsynaptic potential, but not in the sustained slow postsynaptic excitation, and that the release of transmitters from synaptic inputs to AH neurons is frequency coded.

Action Potentials↗