Biomedical subjects

P Jobling

Publications and source records attributed to P Jobling.

16 recordsLinked to original sources

PubMed2004

Differential expression of calcium channels in sympathetic and parasympathetic preganglionic inputs to neurons in paracervical ganglia of guinea-pigs.

Neurons in pelvic ganglia receive nicotinic excitatory post-synaptic potentials (EPSPs) from sacral preganglionic neurons via the pelvic nerve, lumbar preganglionic neurons via the hypogastric nerve or both. We tested the effect of a range of calcium channel antagonists on EPSPs evoked in paracervical ganglia of female guinea-pigs after pelvic or hypogastric nerve stimulation. omega-Conotoxin GVIA (CTX GVIA, 100 nM) or the novel N-type calcium channel antagonist, CTX CVID (100 nM) reduced the amplitude of EPSPs evoked after pelvic nerve stimulation by 50-75% but had no effect on EPSPs evoked by hypogastric nerve stimulation. Combined addition of CTX GVIA and CTX CVID was no more effective than either antagonist alone. EPSPs evoked by stimulating either nerve trunk were not inhibited by the P/Q calcium channel antagonist, omega-agatoxin IVA (100 nM), nor the L-type calcium channel antagonist, nifedipine (30 microM). SNX 482 (300 nM), an antagonist at some R-type calcium channels, inhibited EPSPs after hypogastric nerve stimulation by 20% but had little effect on EPSPs after pelvic nerve stimulation. Amiloride (100 microM) inhibited EPSPs after stimulation of either trunk by 40%, while nickel (100 microM) was ineffective. CTX GVIA or CTX CVID (100 nM) also slowed the rate of action potential repolarization and reduced afterhyperpolarization amplitude in paracervical neurons. Thus, release of transmitter from the terminals of sacral preganglionic neurons is largely dependent on calcium influx through N-type calcium channels, although an unknown calcium channel which is resistant to selective antagonists also contributes to release. Release of transmitter from lumbar preganglionic neurons does not require calcium entry through either conventional N-type calcium channels or the variant CTX CVID-sensitive N-type calcium channel and seems to be mediated largely by a novel calcium channel.

Action Potentials↗

PubMed2001

Differential inhibition by botulinum neurotoxin A of cotransmitters released from autonomic vasodilator neurons.

The role of the soluble NSF attachment protein receptor (SNARE) protein complex in release of multiple cotransmitters from autonomic vasodilator neurons was examined in isolated segments of guinea pig uterine arteries treated with botulinum neurotoxin A (BoNTA; 50 nM). Western blotting of protein extracts from uterine arteries demonstrated partial cleavage of synaptosomal-associated protein of 25 kDa (SNAP-25) to a NH2-terminal fragment of approximately 24 kDa by BoNTA. BoNTA reduced the amplitude (by 70-80%) of isometric contractions of arteries in response to repeated electrical stimulation of sympathetic axons at 1 or 10 Hz. The amplitude of neurogenic relaxations mediated by neuronal nitric oxide (NO) was not affected by BoNTA, whereas the duration of peptide-mediated neurogenic relaxations to stimulation at 10 Hz was reduced (67% reduction in integrated responses). In contrast, presynaptic cholinergic inhibition of neurogenic relaxations was abolished by BoNTA. These results demonstrate that the SNARE complex has differential involvement in release of cotransmitters from the same autonomic neurons: NO release is not dependent on synaptic vesicle exocytosis, acetylcholine release from small vesicles is highly dependent on the SNARE complex, and neuropeptide release from large vesicles involves SNARE proteins that may interact differently with regulatory factors such as calcium.

Acetylcholine↗

PubMed2001

Differential expression of functionally identified and immunohistochemically identified NK(1) receptors on sympathetic neurons.

We have used multiple-labeling immunohistochemistry, intracellular dye-filling, and intracellular microelectrode recordings to characterize the distribution of tachykinin receptors and substance P boutons on subpopulations of neurons within the guinea pig celiac ganglion. Superfusion of substance P (SP, 1 microM for 1 min) depolarized 42% of tonic neurons and inhibited afterhyperpolarizations in 66% of long afterhyperpolarizing (LAH) neurons without significant desensitization. Twenty-one percent of tonic neurons and 24% of LAH neurons responded to the NK(3) agonist senktide but did not respond to SP, indicating SP did not activate NK(3) receptors at this concentration. All effects of SP were abolished by the selective NK(1) receptor antagonist, SR140333, but not by the selective NK(3) receptor antagonist, SR142801, suggesting that exogenous SP activated a receptor with NK(1) pharmacology. No dye-filled LAH neuron and only 50% of tonic neurons responding to SP expressed NK(1) receptor immunoreactivity (NK(1)-IR). All neurons responding to SP had SP immunoreactive fibers within one cell diameter, indicating good spatial matching between SP release sites and target neurons. These results indicate that SP may act via a receptor with NK(1)-like pharmacology that has a C terminus not recognized by antibodies to the intracellular domain of the conventional NK(1) receptor. Inward currents evoked by SP acting on this NK(1)-like receptor or senktide acting through NK(3) receptors had identical current-voltage relationships. In LAH neurons, both agonists suppressed I(sAHP) without reducing I(AHP). Responses evoked by SP and senktide were resistant to PKC inhibitors, suggesting that the transduction mechanisms for the NK(1)-like receptor and the NK(3) receptor may be similar.

Action Potentials↗

PubMed2001

Development of electrophysiological and morphological diversity in autonomic neurons.

The generation of neuronal diversity requires the coordinated development of differential patterns of ion channel expression along with characteristic differences in dendritic geometry, but the relations between these phenotypic features are not well known. We have used a combination of intracellular recordings, morphological analysis of dye-filled neurons, and stereological analysis of immunohistochemically labeled sections to investigate the development of characteristic electrical and morphological properties of functionally distinct populations of sympathetic neurons that project from the celiac ganglion to the splanchnic vasculature or the gastrointestinal tract of guinea pigs. At early fetal stages, neurons were significantly more depolarized at rest compared with neurons at later stages, and they generally fired only a single action potential. By mid fetal stages, rapidly and slowly adapting neurons could be distinguished with a topographic distribution matching that found in adult ganglia. Most rapidly adapting neurons (phasic neurons) at this age had a long afterhyperpolarization (LAH) characteristic of mature vasomotor neurons and were preferentially located in the lateral poles of the ganglion, where most neurons contained neuropeptide Y. Most early and mid fetal neurons showed a weak M current, which was later expressed only by rapidly-adapting and LAH neurons. Two different A currents were present in a subset of early fetal neurons and may indicate neurons destined to develop a slowly adapting phenotype (tonic neurons). The size of neuronal cell bodies increased at a similar rate throughout development regardless of their electrical or neurochemical phenotype or their topographical location. In contrast, the rate of dendritic growth of neurons in medial regions of the ganglion was significantly higher than that of neurons in lateral regions. The apparent cell capacitance was highly correlated with the surface area of the soma but not the dendritic tree of the developing neurons. These results demonstrate that the well-defined functional populations of neurons in the celiac ganglion develop their characteristic electrophysiological and morphological properties during early fetal stages of development. This is after the neuronal populations can be recognized by their neurochemical and topographical characteristics but long before the neurons have finished growing. Our data provide strong circumstantial evidence that the development of the full phenotype of different functional classes of autonomic final motor neurons is a multi-step process likely to involve a regulated sequence of trophic interactions.

Action Potentials↗

PubMed2000

Neuronal morphology and the synaptic organisation of sympathetic ganglia.

In this article, we provide a short review of the structure and synaptic organisation of the final motor neurons in the sympathetic ganglia of mammals. Combinations of pathway tracing, multiple-labelling immunofluorescence and intracellular dye injection have shown that neurons in different functional pathways differ not only in their patterns of neuropeptide expression, but also in the size of their cell bodies and dendritic fields. Thus, vasoconstrictor neurons consistently are smaller than any other major functional class of neurons. Serial section ultrastructural analysis of dye filled neurons, together with electron microscopic and confocal microscopic analysis of immunolabelled synaptic inputs to sympathetic final motor neurons indicate that synapses are rare and randomly distributed over the surface of the neurons. The total number of synapses is simply proportional to the total surface area of the neurons. Many terminal boutons of peptide-containing preganglionic neurons do not make conventional synapses with target neurons. Furthermore, there is a spatial mismatch in the distribution of peptide-containing terminals and neurons expressing receptors for the corresponding peptides. Together, these results suggest that there are likely to be significant differences in the ways that the final sympathetic motor neurons in distinct functional pathways integrate their synaptic inputs. In at least some pathways, heterosynaptic actions of neuropeptides probably contribute to subtle modulation of ganglionic transmission.

Animals↗

PubMed1999

Pathway-specific expression of PKC and PKA in sympathetic neurons.

We used multiple-labelling immunofluorescence, intracellular dye injection, electrophysiological recording and confocal microscopy to examine the expression of immunoreactivity to protein kinase C (PKC) and protein kinase A (PKA) in sympathetic ganglia of guinea-pigs. PKCalpha and PKCgamma were widespread in vasoconstrictor and pilomotor neurons. High levels of PKA RIIalpha and RIIbeta were restricted to neurons that lacked significant expression of PKC, including somatostatin-containing neurons projecting to the gut, and non-noradrenergic vasodilator neurons. In coeliac ganglia, most neurons with PKC contained neuropeptide Y and displayed phasic patterns of action potential firing, often with a long after-hyperpolarization. Tonically firing neurons lacked both neuropeptide Y and PKC. These results show remarkably pathway-specific expression of protein kinases in functionally identified populations of sympathetic neurons.

Action Potentials↗

PubMed1999

Electrophysiological and morphological diversity of mouse sympathetic neurons.

We have used multiple-labeling immunohistochemistry, intracellular dye-filling, and intracellular microelectrode recordings to characterize the morphological and electrical properties of sympathetic neurons in the superior cervical, thoracic, and celiac ganglia of mice. Neurochemical and morphological characteristics of neurons varied between ganglia. Thoracic sympathetic ganglia contained three main populations of neurons based on differential patterns of expression of immunoreactivity to tyrosine hydroxylase, neuropeptide Y (NPY) and vasoactive intestinal peptide (VIP). In the celiac ganglion, nearly all neurons contained immunoreactivity to both tyrosine hydroxylase and NPY. Both the overall size of the dendritic tree and the number of primary dendrites were greater in neurons from the thoracic and celiac ganglia compared with those from the superior cervical ganglion. The electrophysiological properties of sympathetic neurons depended more on their ganglion of origin rather than their probable targets. All neurons in the superior cervical ganglion had phasic firing properties and large afterhyperpolarizations (AHPs). In addition, 34% of these neurons displayed an afterdepolarization preceding the AHP. Superior cervical ganglion neurons had prominent I(M), I(A), and I(H) currents and a linear current-voltage relationship between -60 and -110 mV. Neurons from the thoracic ganglia had significantly smaller action potentials, AHPs, and apparent cell capacitance compared with superior cervical ganglion neurons, and only 18% showed an afterdepolarization. All neurons in superior cervical ganglia and most neurons in celiac ganglia received at least one strong preganglionic input. Nearly one-half the neurons in the celiac ganglion had tonic firing properties, and another 15% had firing properties intermediate between those of tonic and phasic neurons. Most celiac neurons showed significant inward rectification below -90 mV. They also expressed I(A), but with slower inactivation kinetics than that of superior cervical or thoracic neurons. Both phasic and tonic celiac ganglion neurons received synaptic inputs via the celiac nerves in addition to strong inputs via the splanchnic nerves. Multivariate statistical analysis revealed that the properties of the action potential, the AHP, and the apparent cell capacitance together were sufficient to correctly classify 80% of neurons according to their ganglion of origin. These results indicate that there is considerable heterogeneity in the morphological, neurochemical, and electrical properties of sympathetic neurons in mice. Although the morphological and neurochemical characteristics of the neurons are likely to be related to their peripheral projections, the expression of particular electrophysiological traits seems to be more closely related to the ganglia within which the neurons occur.

Action Potentials↗

PubMed1997

Orally projecting interneurones in the guinea-pig small intestine.

1. Orally projecting, cholinergic interneurones are important in mediating ascending excitatory reflexes in the small intestine. We have shown that there is just one major class of orally projecting interneurone, which we have characterized using retrograde labelling in organ culture, combined with immunohistochemistry, intracellular recording and dye filling. 2. Orally projecting interneurones, previously shown to be immunoreactive for choline acetyltransferase, tachykinins, enkephalin, calretinin and neurofilament protein triplet, have axons up to 14 mm long and are the only class of cells with orally directed axons more than 8.5 mm long. 3. They are all small Dogiel type I neurones with short dendrites, usually lamellar in form, and a single axon which sometimes bifurcates. Their axons give rise to short varicose collaterals in myenteric ganglia more than 3 mm oral to their cell bodies. 4. Orally projecting interneurones receive prominent fast excitatory post synaptic potentials (fast EPSPs). A major source of fast EPSPs is other ascending interneurones located further aborally. They also receive fast EPSPs from circumferential pathways. 5. In the stretched preparations used in this study, orally projecting interneurones were highly excitable, firing repeatedly to depolarizing current pulses and had negligible long after-hyperpolarizations following their action potentials. They did not receive measurable non-cholinergic slow excitatory synaptic inputs. 6. Ascending interneurones had a characteristic inflection in their membrane responses to depolarizing current pulses and their first action potential was typically delayed by approximately 30 ms. Under single electrode voltage clamp, ascending interneurones had a transient outward current when depolarized above -70 mV from more hyperpolarized holding potentials. Ascending interneurones also consistently showed marked inward rectification under both current clamp and voltage clamp conditions. 7. This class of cells has consistent morphological, neurochemical and electrophysiological characteristics and are important in mediating orally directed enteric reflexes.

Animals↗

PubMed1996

In vitro relation between preganglionic sympathetic stimulation and activity of cutaneous glands in the bullfrog.

1. Activation of cutaneous glands was studied by measuring changes in transepithelial potentiation (TEP) after pre- and postganglionic sympathetic stimulation in the bullfrog, Rana catesbeiana. 2. In normal Ringer solution, TEP was 20-90 mV with the basolateral (inside) surface positive. Single shocks to the preganglionic B pathway decreased TEP by up to 3 mV. Cutaneous depolarizations had a latency of 1.2 s, a rise time of 2.5 s, and decayed with an exponential time constant of 15 s. Similar depolarizations were evoked by postganglionic stimulation. 3. Cutaneous depolarizations summed during repetitive stimulation and > 0.05 Hz. For trains of three stimuli, peak amplitude increased with frequency and saturated at 2 Hz. In some preparations, longer trains evoked polyphasic changes in TEP. Preganglionically evoked cutaneous responses were abolished by (+)-tubocurarine. Postganglionically evoked cutaneous depolarizations were antagonized by phentolamine, but not propranolol. 4. Repetitive preganglionic stimulation of the C pathway (> 100 at 20 Hz) evoked little change in TEP and did not modulate depolarizations evoked through the B pathway. In nicotine, peptidergic cotransmission was enhanced in the ganglia, and repetitive C pathway stimulation evoked cutaneous depolarizations whose time course mirrored that of the postganglionic peptidergic after-discharge. The after-discharge and associated cutaneous depolarization were blocked by a luteinizing hormone-releasing hormone antagonist. 5. The results show cutaneous glands are selectively innervated by B neurones and respond to low levels of neural activity. Asynchronous postganglionic firing mediated by peptidergic cotransmission can provide a basis for heterosynaptic interactions between the B and C pathways.

Animals↗

PubMed1995

Electrical activity in rat tail artery during asynchronous activation of postganglionic nerve terminals by ciguatoxin-1.

1. The effects of ciguatoxin-1 (CTX-1) on the membrane potential of smooth muscle cells have been examined in rat proximal tail arteries isolated in vitro. 2. CTX-1 (> or = 10 pM) increased the frequency of spontaneous excitatory junction potentials (s.e.j.ps). At 100-400 pM, there was also a marked and maintained depolarization (19.7 +/- 1.4 mV, n = 14, at 400 pM). 3. In 20-400 pM CTX-1, perivascular stimuli evoked excitatory junction potentials (e.j.ps) which were prolonged in time course relative to control. 4. Although threshold and latency of the e.j.p. were not affected by CTX-1 (< or = 400 pM), propagated impulses were blocked at > or = 100 pM. 5. The spontaneous activity and the depolarization produced by CTX-1 were reduced in the presence of Ca2+ (0.1 mM)/Mg2+ (25 mM), omega-conotoxin (0.1 microM) or Cd2+ (50-100 microM). 6. All effects of CTX-1 were abolished by tetrodotoxin (0.3 microM). 7. Raised Ca2+ (6 mM) reduced the depolarization and spontaneous activity produced by CTX-1. 8. In 400 pM CTX-1, the membrane repolarized (17 +/- 3.2 mV, n = 4) following the addition of phentolamine (1 microM). S.e.j.ps and e.j.ps were selectively abolished by suramin (1 mM), and the membrane repolarized by 1.3 +/- 1.6 mV (n = 4). 9. We conclude that CTX-1 releases noradrenaline and ATP by initiating asynchronous discharge of postganglionic perivascular axons. In 100-400 pM CTX-1, the smooth muscle was depolarized to levels resembling those recorded in this artery during ongoing vasoconstrictor discharge in vivo.

Animals↗

PubMed1994

Electrophysiological events during neuroeffector transmission in the spleen of guinea-pigs and rats.

Intracellular recordings were made from smooth muscle cells of arterioles and the capsule of the spleen of guinea-pig and rat, and the responses to periarterial or subcapsular nerve stimulation were recorded. The innervation of the spleen was studied using fluorescence and immunohistochemical techniques. Catecholamine-containing axons were associated with smooth muscle of the splenic capsule, trabeculae, arterioles and amongst cells of the periarteriolar lymphoid sheath. Axons immunoreactive for neuropeptide Y (NPY) and tyrosine hydroxylase were distributed in an identical manner to catecholamine-containing axons, whereas axons immunoreactive for substance P or calcitonin gene-related peptide were present at a very low density in spleens from both species. In segments of arterioles, single transmural stimuli evoked excitatory junction potentials (EJPs) of 1-10 mV amplitude. EJPs facilitated during short trains of stimuli (1-10 Hz) and summated at 10 Hz, often initiating a muscle action potential. EJPs persisted in the presence of prazosin (1 microM) and idazoxan (1 microM), but were abolished by the P2x-purinoceptor antagonist suramin (1 mM). Spontaneous depolarizations were observed in smooth muscle cells of arterioles and capsule. Some events in arterioles were observed in the presence of suramin and so may originate postjunctionally independently of transmitter release. As single transmural stimuli failed to evoke a depolarization in capsular smooth muscle, spontaneous depolarizations in this tissue probably also arise postjunctionally. Short trains of high frequency stimuli (10-35 Hz) evoked biphasic depolarizations of capsular smooth muscle cells. The initial component peaked 2.5 s following the onset of stimulation; the second component peaked 15 s following the onset and decayed exponentially with a time constant of 15 s. By fitting a product of exponentials to the second component, it was possible to define the initial component, which decayed with a time constant of around 1.5 s. Neurally evoked depolarizations of capsular smooth muscle were abolished by 1 microM TTX. Blockade of alpha 1-adrenoceptors with prazosin reduced the initial component of the depolarization, whereas alpha 2-adrenoceptor blockade with idazoxan virtually abolished the second component. In some cells a small, faster depolarization persisted after alpha-adrenoceptor blockade. The slow alpha 2-adrenoceptor-mediated depolarization was identical to that recorded in the rat tail artery and in the guinea-pig mesenteric vein. The data indicate that sympathetic neuroeffector transmission from noradrenergic axons containing NPY to splenic arterial and capsular smooth muscle occur by different mechanisms.

Adrenergic alpha-Antagonists↗

PubMed1994

The sensitivity of nicotinic synapses in bullfrog sympathetic ganglia to alpha-bungarotoxin and neuronal-bungarotoxin.

1. The sensitivity of nicotinic synapses to alpha-bungarotoxin (alpha-Bgt) and neuronal-bungarotoxin (n-Bgt) was measured in the B and C cell systems of bullfrog paravertebral sympathetic ganglia 9 and 10 by recording extracellular compound postganglionic action potentials from the rami communicantes. 2. High concentrations (10 microM) of alpha-Bgt applied for up to 8 h had no effect upon synaptic transmission in either the B or C cell system. Ganglia pretreated with collagenase were also insensitive to alpha-Bgt. In control experiments on isolated sartorius muscle preparations, nerve-evoked twitches were fully blocked by 30-100 nM alpha-Bgt. 3. Nicotinic transmission in the B and C cell systems was reversibly blocked by 30-300 nM n-Bgt. Block appeared within 25-45 min of exposure to toxin and reversed fully with a half-time of 40-80 min. This was indistinguishable from washout times after block by 100 microM (+)-tubocurarine. 4. The results demonstrate close parallels between the bungarotoxin sensitivity of neuronal nicotinic receptors mediating ganglionic transmission in functional subclasses of bullfrog sympathetic neurones and the bungarotoxin sensitivity which has been reported for autonomic in avian and mammalian preparations.

Animals↗

PubMed1993

Calcium induced calcium release is involved in the afterhyperpolarization in one class of guinea pig sympathetic neurone.

The mechanisms underlying two potassium conductances which are activated by Ca2+ influx during the action potential in sympathetic prevertebral neurones of guinea pigs have been investigated pharmacologically. One Ca-activated K+ conductance, which is present in all mammalian sympathetic postganglionic neurones, is maximal after the action potential and decays exponentially with a time constant of about 130 ms; this conductance was inhibited by apamin (50-100 nM) consistent with the involvement of SK channels. A second Ca-activated K+ conductance with much slower kinetics is present in a large subpopulation of coeliac neurones. This conductance was resistant to apamin but markedly inhibited by application of ryanodine (5-20 microM), suggesting that Ca2+ influx during the action potential triggers release of Ca2+ from intracellular stores which in turn activates a different class of K+ channel. Noradrenaline (100 microM) depressed the second K+ conductance selectively.

Action Potentials↗

PubMed1992

An electrophysiological study of responses evoked in isolated segments of rat tail artery during growth and maturation.

1. Intracellular recordings from the smooth muscle of isolated segments of the main caudal artery of rats at various ages between 45 and 150 days postnatal were made in order to relate the spontaneous depolarizations and responses to perivascular stimulation at different levels along the artery to the differences in vessel structure and innervation density during growth of the animals. 2. In the outermost smooth muscle cells close to the neuromuscular junctions, spontaneous depolarizations with fast time courses (spontaneous excitatory junction potentials or SEJPs) were recorded. In cells lying deeper in the media, spontaneous depolarizations had a wide range of time courses and amplitudes, but only a few of those could be attributed to electrotonic attenuation of SEJPs. 3. In arterial segments taken from animals of all ages, stimuli which evoked maximal amplitude excitatory junction potentials (EJPs) 1-2 mm caudal to a suction electrode also evoked neurogenic alpha-depolarizations (NADs) with time to peak of 15 s and duration nearly 1 min. Both responses decreased progressively in amplitude along the length of the artery. NADs were blocked by phentolamine (10(-6) M) or idazoxan (10(-7) M) which were without effects on EJPs. 4. During short trains of stimuli (5 at 1 or 10 Hz), EJPs facilitated but to a lesser extent with distance along the tail. Such trains evoked NADs of greater amplitude than those following a single stimulus; these were often preceded by contractions of the artery which were restricted to the region close to the stimulating electrode. 5. Increasing stimulus voltage led to progressive prolongation of the decay phase of the EJP. After the addition of tetrodotoxin (10(-7) M), or in the presence of reduced Ca2+ and raised Mg2+ concentration, slow depolarizing potentials (SDPs) (with time to peak of 150-300 ms and decay lasting > 2 s) were recorded which were graded in amplitude with stimulus voltage. SDPs were attenuated by increasing Ca2+ concentration to 5 mM. These responses often added to the EJP at supramaximal stimulus voltages. 6. The mean amplitudes of the EJP and NAD declined significantly with age, the former to a greater degree than the latter. These changes may be explained by changes in the electrical properties of the media related to hypertrophy of smooth muscle cells as the animals grew, and emphasize the need to allow for such growth effects in studies of young rats.(ABSTRACT TRUNCATED AT 400 WORDS)

Adrenergic Fibers↗

PubMed1992

Electrophysiological responses in the rat tail artery during reinnervation following lesions of the sympathetic supply.

1. Responses to perivascular stimuli have been recorded with intracellular microelectrodes from the smooth muscle of isolated segments of the main caudal artery of rats at various times between 7 and 128 days after all four collector nerve trunks had been lesioned near the base of the tail at 21 days of age. 2. In proximal segments (< 40 mm distal to the lesions), excitatory junction potentials (EJPs) and neurogenic alpha-depolarizations (NADs) evoked by stimuli presented via a proximally located suction electrode were similar to those in the same segments of unoperated control animals of the same age. Supramaximal EJPs in these segments decreased in amplitude with age. 3. Stimuli just supramaximal for EJPs in innervated preparations failed to evoke responses in segments farther than 30-40 mm distal to the lesions at any time after the nerves had been cut and 1 cm excised. Higher voltages evoked slow depolarizing potentials (SDPs) which were of longer time course than EJPs. Similar responses occurred in segments over 60 mm distal to the lesions at 20-50 days after the nerves had been frozen, and in all segments sampled over 100 mm distal to nerve lesions. 4. Spontaneous transient depolarizations (STDs) were recorded at all depths of the media in denervated segments. These occurred at frequencies similar to those of spontaneous events (including attenuated spontaneous EJPs) in innervated segments. 5. The earliest signs of reinnervation (24-42 days after freeze lesions) consisted of very small amplitude EJPs of normal time course which facilitated markedly during a short train of stimuli (5-10 Hz); these were followed by NADs which were large relative to the amplitudes of the EJPs. Less commonly, small focal EJPs of brief time course (resembling spontaneous EJPs in superficial cells of innervated arteries) were evoked in very restricted regions of the vessel wall. 6. At later times (57-128 days postoperative), six of eight segments located 40-70 mm distal to freeze lesions showed EJPs of nearly control amplitude, but NADs that were larger than in equivalent segments from control animals. In the remaining two cases, reinnervation at this level was similar to that seen at the earliest postoperative times. High stimulus voltages prolonged the decay of EJPs in both control and reinnervated arteries. 7. Sensitivity to exogenous noradrenaline, assessed in terms of membrane depolarization, was increased in both denervated and reinnervated segments. 8. Catecholamine fluorescence disappeared from the arteries at a distance greater than 30-40 mm distal to the site of the nerve lesions.(ABSTRACT TRUNCATED AT 400 WORDS)

Adrenergic Fibers↗

PubMed1989

The distribution of gamma-adrenoceptors and P2 purinoceptors in mesenteric arteries and veins of the guinea-pig.

1. Membrane potential changes and contractions were recorded from mesenteric arteries and veins of the guinea-pig, during perivascular nerve stimulation or application of noradrenaline or adenosine triphosphate (ATP). 2. After alpha-adrenoceptor blockade, noradrenaline activated low affinity adrenoceptors (gamma-adrenoceptors) causing depolarization and arterial contraction only in the presence of an inhibitor of catecholamine uptake. 3. Noradrenaline did not cause depolarization or contraction of the vein after alpha-adrenoceptor blockade even after catecholamine uptake was blocked. 4. Adenosine triphosphate caused depolarization and contraction of both arteries and veins. These responses were abolished by alpha-,beta-,methylene adenosine triphosphate (Me-ATP). 5. Me-ATP abolished rapid excitatory junction potentials (e.j.ps) caused by perivascular nerve stimulation of arteries but had no effect on arterial responses mediated by gamma-adrenoceptors. 6. In veins, perivascular nerve stimulation evoked slow e.j.ps which persisted in the presence of Me-ATP but were abolished after blockade of alpha-adrenoceptors. 7. The observations indicate that P2 purinoceptors are present on both mesenteric artery and vein whilst gamma-adrenoceptors are localized near the neuromuscular junction of the artery. However gamma-adrenoceptors do not appear to be directly involved in the generation of arterial e.j.ps.

Adenosine Triphosphate↗