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W F Colmers

Publications and source records attributed to W F Colmers.

At least 37 records · Page 2Linked to original sources
PubMed1991

Neuropeptide Y inhibits Ca2+ influx into cultured dorsal root ganglion neurones of the rat via a Y2 receptor.

1. The identity of the neuropeptide Y (NPY) receptor associated with the observed inhibition of neuronal Ca2+ currents (ICa) in rat dorsal root ganglion (DRG) cells has been established on the basis of agonist responses to analogues and carboxy terminal (C-terminal) fragments of the NPY molecule. 2. Whole cell barium currents (IBa) in DRG cells were reversibly inhibited by 100 nM NPY, 100 nM PYY and C-terminal fragments of NPY in a manner that correlated with the length of the NPY fragments (for inhibition of the IBa NPY = PYY greater than NPY2-36 greater than NPY13-36 greater than NPY16-36 greater than NPY18-36 much greater than NPY25-36). 3. C-terminal fragments of NPY were also effective in reversibly reducing the ICa, the associated increase in the intracellular Ca2+ concentration [( Ca2+]i) and the increased [Ca2+]i produced by evoked action potentials in the DRG cells. In addition, a Ca(2+)-activated Cl- conductance was also reversibly reduced by NPY fragments only when accompanied by a reduction in Ca2+ entry. 4. We conclude that the Y2 receptor for neuropeptide Y is coupled to inhibition of Ca2+ influx via voltage-sensitive calcium channels in DRG cells.

Action Potentials↗
PubMed1991

Presynaptic inhibition by neuropeptide Y in rat hippocampal slice in vitro is mediated by a Y2 receptor.

1. The action of analogues and C-terminal fragments of neuropeptide Y (NPY) was examined on excitatory synaptic transmission in area CA1 of the rat hippocampal slice in vitro, by use of intracellular and extracellular recordings, to determine by agonist profile the NPY receptor subtype mediating presynaptic inhibition. 2. Neither NPY, analogues nor fragments of NPY affected the passive or active properties of the post-synaptic CA1 pyramidal neurones, indicating their action is at a presynaptic site. 3. The full-sequence analogues, peptide YY (PYY) and human NPY (hNPY), were equipotent with NPY at the presynaptic receptor, while desamido hNPY was without activity. 4. NPY2-36 was equipotent with NPY. Fragments as short as NPY 13-36 were active, but gradually lost activity with decreasing length. NPY 16-36 had no effect on extracellular field potentials, but still significantly inhibited excitatory postsynaptic potential amplitudes. Fragments shorter than NPY 16-36 had no measurable effect on synaptic transmission. 5. The presynaptic NPY receptor in hippocampal CA1 therefore shares an identical agonist profile with the presynaptic Y2 receptor at the peripheral sympathetic neuroeffector junction.

Action Potentials↗
PubMed1989

Presynaptic inhibition by neuropeptide Y and baclofen in hippocampus: insensitivity to pertussis toxin treatment.

Neuropeptide Y (NPY) presynaptically inhibits excitatory transmission in area CA1 of rat hippocampus. As postsynaptic NPY receptors in certain other tissues have been shown to be coupled to G-proteins, we have tested the hypothesis that the hippocampal NPY effects are also mediated by G-proteins. Pretreatment of rats with pertussis toxin (PTX) was ineffective in blocking NPY's presynaptic inhibitory actions in area CA1 of the hippocampal slice. The presynaptic inhibitory action of baclofen was also unaffected by PTX pretreatment. However, in these same PTX-pretreated slices, the postsynaptic hyperpolarizing actions of baclofen and 5-hydroxytryptamine were blocked. We suggest that pre- and postsynaptic receptors possess different coupling mechanisms to their effectors.

Animals↗
PubMed1989

5-HT-mediated synaptic potentials in the dorsal raphe nucleus: interactions with excitatory amino acid and GABA neurotransmission.

1. Intracellular recordings from neurons within dorsal raphe nucleus in slices from rat brain were used to study an inhibitory postsynaptic potential (IPSP) evoked by electrical stimulation. 2. The IPSP was observed in approximately 70% of neurons, had a latency to onset of 40-65 ms, reached a peak in 350-400 ms, had a total duration of 1-2 s, and reversed polarity at the potassium equilibrium potential. 3. This IPSP was blocked by spiperone (1 microM) and prolonged by fluoxetine (300 nM-30 microM) suggesting that it was mediated by 5-hydroxytryptamine (5-HT). 4. Superfusion with gamma-aminobutyric acid (GABA) and excitatory amino acid receptor antagonists were used to block "fast" synaptic potentials that preceded the IPSP such that it could be studied in isolation. Blockade of the GABA-mediated synaptic potentials increased the amplitude of the IPSP by 1.3-fold. The amplitude of the IPSP was reduced by 30% after blockade of the excitatory amino acid-mediated synaptic potential. 5. The results indicate that the IPSP recorded in dorsal raphe neurons was caused by 5-HT released at least in part from indirect (synaptically induced) excitation of 5-HT-containing cells within the slice.

Animals↗
PubMed1988

Pertussis toxin pretreatment discriminates between pre- and postsynaptic actions of baclofen in rat dorsal raphe nucleus in vitro.

Intracellular recordings were made from rat dorsal raphe neurons in vitro. Baclofen (30 microM) and 5-carboxamidotryptamine (5-CT, 300 nM to 1 microM) hyperpolarized these neurons by 10 and 13 mV, respectively. Depolarizing synaptic potentials (DSPs) were evoked by single shocks: baclofen reduced the amplitude of the DSP by 81%, but 5-CT reduced it by only 23%. The somatic response to iontophoretically applied glutamate pulses was reduced by 12% by baclofen, and 23% by 5-CT. In slices from rats pretreated with intracerebroventricular pertussis toxin (PTX), the ability of baclofen to reduce the DSP was almost unchanged, although the hyperpolarizing action of baclofen, and both actions of 5-CT were virtually eliminated. We conclude that it is possible to distinguish the pre- and postsynaptic actions of baclofen with PTX, and that the actions of 5-CT are both blocked.

Animals↗
PubMed1988

Neuropeptide Y action in the rat hippocampal slice: site and mechanism of presynaptic inhibition.

Neuropeptide Y (NPY), the most abundant peptide in mammalian CNS, has been shown to inhibit excitatory neurotransmission presynaptically at the stratum radiatum-CA1 synapse in the in vitro rat hippocampal slice. We examined the site and mechanism of this inhibition in a series of in vitro intra- and extracellular recordings in areas CA1 and CA3, the source of much of the excitatory synaptic input to the CA1 neurons. NPY's inhibitory action at the stratum radiatum-CA1 synapse was unaffected by high concentrations of the antagonists bicuculline, theophylline, or atropine, suggesting that it does not act by stimulating the release of the known presynaptic inhibitory transmitters GABA, adenosine, or ACh, respectively. Bath application of 10(-6) NPY, a concentration that strongly inhibited the stratum radiatum-CA1 synapse had no effect on CA3 neuron resting potential, input resistance or action potential amplitude, threshold, or duration. NPY also does not alter the amplitude or duration of the prolonged CA3 action potentials evoked in the presence of TTX, tetraethyl-ammonium, and elevated external Ca2+ or those evoked in the presence of TTX and Ba2+ ions. NPY therefore does not alter the passive or active properties of the somata of the presynaptic CA3 neurons. Neither the afferent fiber volley of the Schaffer collaterals in stratum radiatum of area CA1 nor the excitability of the CA3 terminals in CA1 was affected by NPY application. However, application of the transient K+ current blocker, 4-aminopyridine (4-AP) at concentrations of 10 and 50 microM, completely abolished the action of 10(-6) M NPY on the stratum radiatum-CA1 excitatory synaptic potentials. This action of 4-AP could be reversed by reducing extracellular Ca2+ concentrations from a control level of 1.5 to 0.7 mM (in 10 microM 4-AP) and to 0.5 mM (in 50 microM 4-AP). The evidence suggests that NPY inhibits excitatory synaptic transmission at the Schaffer collateral-CA1 synapse by acting directly at the terminal to reduce a Ca2+ influx.

Acetylcholine↗
PubMed1988

Voltage- and ligand-activated inwardly rectifying currents in dorsal raphe neurons in vitro.

Intracellular recordings were made from neurons in rat dorsal raphe in the slice preparation maintained at 37 degrees C. The single-electrode voltage-clamp method was used to measure membrane currents at potentials more negative than rest (-60 mV). Three types of inward rectification were observed: 2 in the absence of any drugs and the third induced by 5-HT 1 and GABA-B receptor agonists. In the absence of any drugs, an inward current activated over 1-2 sec when the membrane potential was stepped to potentials more negative than -70 mV. This current was blocked by cesium (2 mM) and resembles IQ or IH. A second inward current (IIR) occurred at membrane potentials near the potassium equilibrium potential (EK). This inward current activated within the settling time of the clamp and was abolished by both barium (10-100 microM) and cesium (2 mM). 5-HT 1 agonists activated a potassium conductance that hyperpolarized the cells at rest. This potassium conductance was about 2 nS at -60 mV and increased linearly with membrane hyperpolarization to about 4 nS at -120 mV. Baclofen activated a potassium conductance identical in amplitude and voltage dependence to that induced by 5-HT 1 agonists. Both the baclofen- and 5-HT-induced currents were nearly abolished in animals pretreated with pertussis toxin. The results indicate that a common potassium conductance is increased by 5-HT acting on 5-HT 1 receptors and baclofen acting on GABA-B receptors. This potassium conductance rectifies inwardly and is distinct from the Q-current. The ligand-activated potassium conductance also differs from the other form of inward rectification (IIR) in its voltage dependence and sensitivity to pertussis toxin.

Animals↗
PubMed1987

Endogenous peptides work at multiple sites in the nervous system in the control of gill behaviors in Aplysia.

The suprafusion of two endogenous neuropeptides, arginine vasotocin (AVT) and small cardioactive peptide B (SCPB), over the abdominal ganglion of Aplysia californica significantly affects the ability of a central gill motor neuron to elicit a gill withdrawal response. Gill motor neurons L7 or LDG1 were depolarized to produce the same number of action potentials (APs) on each trial. When AVT (10(-6)M) was suprafused, the motor neurons' ability to elicit a gill movement was suppressed; while SCPB (10(-6)M) superfusion facilitated the response. Neither peptide altered the passive membrane properties of the motor neurons nor did they affect the duration of their APs. These results are consistent with the hypothesis that the peptides act via central control neurons which exert both suppressive and facilitatory control over gill reflex behaviors and associated neural activity.

Animals↗
PubMed1987

Presynaptic action of neuropeptide Y in area CA1 of the rat hippocampal slice.

1. Neuropeptide tyrosine (neuropeptide Y, NPY), a recently isolated endogenous brain peptide, reduces the extracellular population spike evoked by stimulation of stratum radiatum in area CA1 of the in vitro rat hippocampal slice, without reducing the antidromically evoked population spike. To test the hypothesis that NPY acts presynaptically, intracellular recordings were made of pyramidal neurones of area CA1 in vitro. 2. Bath application of 10(-6) M-NPY causes a long-lasting (1-1.5 h), reversible reduction of the orthodromically evoked excitatory post-synaptic potential (e.p.s.p.) recorded intracellularly from CA1 pyramidal neurones. This effect on the e.p.s.p. was dependent upon the concentration of NPY. 3. The resting membrane potential, slope input resistance, and action potential threshold, amplitude and duration of the CA1 pyramidal neurones were not affected by NPY. 4. The responses of CA1 pyramidal neurones to ionophoretic pulses of glutamate, applied to the dendrites during synaptic blockade, was also unaffected by NPY. 5. The evidence supports the hypothesis that NPY acts presynaptically in the CA1 region of hippocampus to reduce excitatory input to the pyramidal neurones.

Action Potentials↗
PubMed1985

Neuropeptide Y reduces orthodromically evoked population spike in rat hippocampal CA1 by a possibly presynaptic mechanism.

Application of the brain neuropeptide Y (NPY) to rat hippocampus in vitro reversibly reduced the amplitude of the CA1 population spike evoked by stratum radiatum stimulation. Threshold for the effect was 10(-8) M. NPY had similar effects on single pulse- and paired pulse-evoked population spikes. Antidromic population spikes, evoked from the alveus, were unaffected by NPY. Thus, NPY appears to modulate excitatory transmission in the hippocampus by a presynaptic mechanism.

Animals↗
PubMed1985

Electron-microscopic observations of the gravity receptor epithelia of normal and spinner juvenile Octopus maya.

Light and electron microscopy of the gravity receptor epithelia (maculae) of statocysts of normal and "spinner" juvenile Octopus maya showed differences between the structures of the hair cells, supporting cells, and afferent neurons of these cephalopods. The maculae of spinner animals were approximately 30% smaller in their surface area and had 40% fewer hair cells. Moreover, the average distance between randomly-chosen hair bundles in scanning electron micrographs of maculae of normal animals was significantly greater (4.33 +/- 6.47 microns) than those of maculae of spinner animals (3.38 +/- 4.90 microns; P less than 0.0001). The sectional area of the supporting cell's microvilli in spinner maculae was larger (0.16 +/- 0.18 microns) than those of normal (0.10 +/- 0.10 micron; P less than 0.0001) O. maya. The morphological differences observed between certain structural components of the maculae of normal and spinner O. maya may be related to the absence and/or malformation of the neuroepithelial suprastructures in spinners. This may have direct or indirect effects to their inability to orient to gravity with these organs.

Acoustic Maculae↗
PubMed1985

The effects of small cardioactive peptide B on the isolated heart and gill of Aplysia californica.

Effects of small cardioactive peptide B on the physiology of the isolated heart and gill preparations from the mollusc Aplysia californica were examined. In addition, the effects of small cardioactive peptide B and FMRFamide (Phe-Met-Arg-Phe-NH2) on adenylate cyclase activity were compared in particulate fractions of heart and gill tissues, respectively. Small cardioactive peptide B was found to exert dose-dependent, reversible changes in cardiac activity when perfused through the isolated heart. The EC50 values effecting changes in heart rate and force of contraction were 3 X 10(-11) and 3 X 10(-10) M, respectively; minimum concentrations found to effect changes in heart rate and force of contraction were normally 10(-15) and 10(-12) M, respectively. However, some winter hearts demonstrated threshold sensitivity to small cardioactive peptide B at concentrations as low as 10(-17) M. When perfused through the isolated gill, small cardioactive peptide B was found to suppress the gill withdrawal response amplitude with a threshold concentration of 10(-14) M and an EC50 value of 3 X 10(-11) M. Suppression of the gill withdrawal response amplitude by small cardioactive peptide B was found to be dose dependent and reversible up to a concentration of 10(-9) M. At higher concentrations, the suppression tended to persist irreversibly. Small cardioactive peptide B stimulated adenylate cyclase activity in particulate fractions of both heart and gill tissues with an EC50 of 0.1 and 1.0 microM, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenylyl Cyclases↗
PubMed1984

"Spinner" cephalopods: defects of statocyst suprastructures in an invertebrate analogue of the vestibular apparatus.

Individuals of seven species of coleoid cephalopods (three species of octopus, three of squid, and one of cuttlefish), that were cultured and reared in laboratory aquarium systems, had a behavioral defect at hatching which was characterized by an inability to control orientation while swimming. These defective animals were designated as "spinners." An examination of statocysts from individuals of five of the affected species revealed abnormalities of the neuro-epithelial suprastructures: absence or malformation of the statolith of the gravity receptor system and absence of the cupulae of the angular acceleration receptor systems. The sensory epithelia did not differ from those of normal animals, nor did the synaptic structures and relationships, when examined both with scanning and transmission electron microscopy. The abnormalities were compared with congenital defects of the neuropeithelial suprastructures of the vestibular apparatus (especially in mammals). The defects observed in statocysts of spinner animals are thought to be the result of environmental causes, such as the temperature or chemistry of the seawater in the transportation vessels or rearing systems, rather than genetic causes.

Animals↗
PubMed1982

The central afferent and efferent organization of the gravity receptor system of the statocyst of Octopus vulgaris.

In Octopus vulgaris, the projections of the afferent fibers from, and the locations of cell bodies of the efferent fibers of, the nerve innervating and macula (statocyst gravity receptor epithelium) were studied within the CNS using iontophoretic whole nerve injection of either cobalt chloride or Lucifer Yellow CH.13 Afferent fibers from the macula nerve project to subesophageal, periesophageal and supraesophageal areas of the brain. Large numbers of such fibers were found in the subeosophageal lateral pedal and posterior lateral pedal lobes, palliovisceral lobe, and the magnocellular commissure. Afferent fibers were also found in the periesophageal ventral and dorsal magnocellular lobes. Supraesophageal macular nerve afferent projections were seen to the peduncle lobe and the ipsilateral median basal lobe. There is evidence for two different macular nerve afferent projections to the contralateral median basal lobe, via and suprapedal commissure and the macula-to-contralateral-median-basal-lobe tract. Evidence is presented for the location of at least some of the macula's efferent fiber's cell bodies in the lateral and posterior lateral pedal lobes, and magnocellular lobes. The differences between the results obtained here with the two different staining methods are discussed. The results imply that processing of static information occurs in many areas of the Octopus CNS, and is much more complex than previously thought. Some of the possible physiological consequences are considered.

Afferent Pathways↗
PubMed1981

Afferent synaptic connections between hair cells and the somata of intramacular neurons in the gravity receptor system of the statocyst of Octopus vulgaris.

In the sensory epithelium (macula) of the gravity receptor system of the statocyst of Octopus vulgaris, there are two types of afferent neurons, distinguished according to their position in the epithelium. The somata of one type lie accumulated in a ring peripheral to the hair cell layer of the epithelium; these are designated as perimacular neurons. The somata of the other type lie among the hair cells, below the level of their nuclei; these are designated as intramacular neurons. Axons of afferent neurons which touch the hair cells are postsynaptic to some of the hair cells touched. As the somata of the intramacular neurons also touch the hair cells, they were investigated by serial electron microscopic reconstruction to determine if afferent synaptic contacts between hair cells and these somata occur. An average of about 600 intramacular neurons was counted in two maculae. Afferent synapses were seen to occur between hair cells and the somata of 76% of the intramacular neurons investigated. The postsynaptic processes of the intramacular neurons' somata were of two morphological types; one with a finger-like and one with a flat postsynaptic process (average of one synapse of each type per soma). The soma of an intramacular neurons can be postsynaptic to more than one hair cell simultaneously (average of 1--2 hair cells per soma). In addition to being presynaptic to only one neuron's soma, a hair cell could be simultaneously presynaptic to the axons of one or more afferent neurons. The morphological findings are discussed as to their possible physiological consequences.

Afferent Pathways↗
PubMed1981

Diphenylhydantoin enhances early adaptation in Aplysia giant neurons.

Diphenylhydantoin effect on excitability in the molluscan giant neuron was investigated. This model of neuronal excitability was convenient for investigating drug mechanisms because the giant somata of these neurons have multiple current systems and can be voltage clamped. Current and voltage clamp methods were used to quantitate firing frequency and the slow membrane currents associated with changes in firing rate. Diphenylhydantoin enhanced the early rapid deceleration of firing of the cell in response to depolarizing current and blocked an early show inward current.

Action Potentials↗