Role of cyclooxygenase activation and prostaglandins in antigen-induced excitability changes of bronchial parasympathetic ganglia neurons

2003 ◽  
Vol 284 (4) ◽  
pp. L581-L587 ◽  
Author(s):  
Radhika Kajekar ◽  
Bradley J. Undem ◽  
Allen C. Myers

In vitro antigen challenge has multiple effects on the excitability of guinea pig bronchial parasympathetic ganglion neurons, including depolarization, causing phasic neurons to fire with a repetitive action potential pattern and potentiating synaptic transmission. In the present study, guinea pigs were passively sensitized to the antigen ovalbumin. After sensitization, the bronchi were prepared for in vitro electrophysiological intracellular recording of parasympathetic ganglia neurons to investigate the contribution of cyclooxygenase activation and prostanoids on parasympathetic nerve activity. Cyclooxygenase inhibition with either indomethacin or piroxicam before in vitro antigen challenge blocked the change in accommodation. These cyclooxygenase inhibitors also blocked the release of prostaglandin D2 (PGD2) from bronchial tissue during antigen challenge. We also determined that PGE2 and PGD2 decreased the duration of the action potential after hyperpolarization, whereas PGF2α potentiated synaptic transmission. Thus prostaglandins released during antigen challenge have multiple effects on the excitability of guinea pig bronchial parasympathetic ganglia neurons, which may consequently affect the output from these neurons and thereby alter parasympathetic tone in the lower airways.

1999 ◽  
Vol 82 (2) ◽  
pp. 818-828 ◽  
Author(s):  
Philip J. Davies ◽  
David R. Ireland ◽  
Juan Martinez-Pinna ◽  
Elspeth M. McLachlan

The electrophysiological consequences of blocking Ca2+ entry through L-type Ca2+ channels have been examined in phasic ( Ph), tonic ( T), and long-afterhyperpolarizing ( LAH) neurons of intact guinea pig sympathetic ganglia isolated in vitro. Block of Ca2+entry with Co2+ or Cd2+ depolarized T and LAH neurons, reduced action potential (AP) amplitude in Ph and LAHneurons, and increased AP half-width in Ph neurons. The afterhyperpolarization (AHP) and underlying Ca2+-dependent K+ conductances ( gKCa1 and gKCa2) were reduced markedly in all classes. Addition of 10 μM nifedipine increased input resistance in LAHneurons, raised AP threshold in Ph and LAH neurons, and caused a small increase in AP half-width in Ph neurons. AHP amplitude and the amplitude and decay time constant of gKCa1 were reduced by nifedipine in all classes; the slower conductance, gKCa2, which underlies the prolonged AHP in LAH neurons, was reduced by 40%. Surprisingly, AHP half-width was lengthened by nifedipine in a proportion of neurons in all classes; despite this, neuron excitability was increased during a maintained depolarization. Nifedipine’s effects on AHP half-width were not mimicked by 2 mM Cs+ or 2 mM anthracene-9-carboxylic acid, a blocker of Cl− channels, and it did not modify transient outward currents of the A or D types. The effects of 100 μM Ni2+ differed from those of nifedipine. Thus in Ph neurons, Ca2+ entry through L-type channels during a single action potential contributes to activation of K+ conductances involved in both the AP and AHP, whereas in T and LAH neurons, it acts only on gKCa1 and gKCa2. These results differ from the results in rat superior cervical ganglion neurons, in which L-type channels are selectively coupled to BK channels, and in hippocampal neurons, in which L-type channels are selectively coupled to SK channels. We conclude that the sources of Ca2+ for activating the various Ca2+-activated K+conductances are distinct in different types of neuron.


1996 ◽  
Vol 270 (4) ◽  
pp. L630-L636 ◽  
Author(s):  
A. C. Myers ◽  
B. J. Undem

Muscarinic receptor regulation of synaptic transmission in guinea pig bronchial parasympathetic ganglia was evaluated with the use of intracellular recording of the intrinsic ganglion neurons. Methacholine (1 microM) decreased the amplitude of vagus nerve-stimulated fast excitatory postsynaptic potentials (fEPSP) by 33 and 46% (at 0.8 and 8.0 Hz, respectively) but had no effect on the amplitude of the depolarizations evoked by a bath-applied nicotinic receptor agonist. Methoctramine (1 microM) inhibited methacholine's effect on fEPSP but alone did not influence the magnitude of the fEPSP evoked by vagus nerve stimulation. Methacholine (10 microM) depolarized a subpopulation of neurons (approximately 4 mV), which was blocked by pirenzepine (0.1 microM). In other neurons, either no effect or a small (1-5 mV) hyperpolarization was noted. Cholinergic contractions of bronchial smooth muscle elicited by electrical field stimulation were potentiated by methoctramine to the same extent as those evoked by vagus nerve (preganglionic) stimulation. The data indicate that M2 receptor activation can lead to inhibition of presynaptic acetylcholine release and consequently a significant inhibition of synaptic transmission in bronchial parasympathetic ganglia. The physiological role of this neuromodulatory effect appears limited, however, when studied in the in vitro setting.


1991 ◽  
Vol 71 (3) ◽  
pp. 970-976 ◽  
Author(s):  
A. C. Myers ◽  
B. J. Undem ◽  
D. Weinreich

The bronchus was isolated from actively sensitized guinea pigs, and the effect of antigen challenge on the excitability of bronchial parasympathetic ganglion neurons was examined with standard intracellular recording techniques. Based on histological examination, we found that mast cells were located near parasympathetic ganglia neurons. Antigen challenge resulted in a loss of mast cell staining and the release of the mast cell-associated mediators, histamine (38 ng/g, approximately 14% of total content) and prostaglandin D2 (PGD2, 118 ng/g wet weight of tissue). Challenging the isolated bronchus with the sensitizing antigen resulted in a transient depolarization (mean 6 mV) of the resting membrane potential of the neurons. Antigen challenge also had a dramatic effect on the accommodative properties of the neurons. Before antigen challenge, two subpopulations of neurons could be differentiated by their response to cathodal current steps: 60% of the cells responded in a “phasic” manner, firing one to six spikes and then accommodated, whereas the balance fired spikes repetitively throughout the current pulse. In phasic firing cells, ovalbumin challenge produced a decrease in accommodation. This was evidenced by a fivefold increase in the number of action potentials elicited during a 500-ms suprathreshold current pulse. The antigen-induced depolarization could be mimicked by histamine, whereas the decrease in accommodation was mimicked by application of PGD2. Leukotriene C4, another mast cell-associated mediator, had no effect on these neuronal properties. These results provide evidence that the immediate hypersensitivity response in guinea pig airways may involve changes in membrane characteristics of bronchial parasympathetic ganglia neurons.


2001 ◽  
Vol 40 (6) ◽  
pp. 806-817 ◽  
Author(s):  
Karen A Maubach ◽  
Karine Martin ◽  
David W Smith ◽  
Louise Hewson ◽  
Robert A Frankshun ◽  
...  

1993 ◽  
Vol 69 (2) ◽  
pp. 626-629 ◽  
Author(s):  
J. C. Behrends ◽  
G. ten Bruggencate

1. The effect of cholinergic receptor activation on gamma-aminobutyric acid (GABA)-mediated inhibitory synaptic transmission was investigated in voltage-clamped CA1 pyramidal neurons (HPNs) in the guinea pig hippocampal slice preparation. 2. The cholinergic agonist carbachol (1-10 microM) induced a prominent and sustained increase in the frequency and amplitudes of spontaneous inhibitory postsynaptic currents (IPSCs) in Cl(-)-loaded HPNs. The potentiation of spontaneous IPSCs was not dependent on excitatory synaptic transmission but was blocked by atropine (1 microM). 3. Monosynaptically evoked IPSCs were reversibly depressed by carbachol (10 microM). 4. The frequency of miniature IPSCs recorded in the presence of tetrodotoxin (0.6 or 1.2 microM) was reduced by carbachol (10 or 20 microM) in an atropine-sensitive manner. 5. We conclude that, while cholinergic receptor activation directly excites hippocampal GABAergic interneurons, it has, in addition, a suppressant effect on the synaptic release mechanism at GABAergic terminals. This dual modulatory pattern could explain the suppression of evoked IPSCs despite enhanced spontaneous transmission.


1990 ◽  
Vol 259 (6) ◽  
pp. L403-L409 ◽  
Author(s):  
A. C. Myers ◽  
B. J. Undem ◽  
D. Weinreich

Active and passive membrane membrane properties of parasympathetic neurons were examined in vitro in a newly localized ganglion on the right bronchus of the guinea pig. Neurons could be classified as “tonic” or “phasic” based on their action potential discharge response to suprathreshold depolarizing constant current steps. Tonic neurons (39%) responded with repetitive action potentials sustained throughout the current step, whereas phasic neurons (61%) responded with an initial burst of action potentials at the onset of the step but then accommodated. Tonic and phasic neurons could not be differentiated by other active or passive membrane properties. Electrical stimulation of the vagus nerve elicited one to three temporally distinct fast nicotinic excitatory potentials, and tetanic stimulation of the vagus nerve evoked slow depolarizing (10% of neurons) and hyperpolarizing (25% of neurons) potentials; the latter was mimicked by muscarinic receptor activation. Similar slow and fast postsynaptic potentials were observed in both tonic and phasic neurons. We suggest neurons within the bronchial ganglion possess membrane and synaptic properties capable of integrating presynaptic stimuli.


1994 ◽  
Vol 71 (2) ◽  
pp. 561-574 ◽  
Author(s):  
E. P. Christian ◽  
J. Togo ◽  
K. E. Naper

1. Intracellular recordings were made from C-fiber neurons identified by antidromic conduction velocity in intact guinea pig nodose ganglia maintained in vitro, and whole-cell patch clamp recordings were made from dissociated guinea pig nodose neurons to investigate the contribution of various K+ conductances to action-potential repolarization. 2. The repolarizing phase of the intracellularly recorded action potential was prolonged in a concentration-dependent manner by charybdotoxin (Chtx; EC50 = 39 nM) or iberiatoxin (Ibtx; EC50 = 48 nM) in a subpopulation of 16/36 C-fiber neurons. In a subset of these experiments, removal of extracellular Ca2+ reversibly prolonged action-potential duration (APD) in the same 4/9 intracellularly recorded C-fiber neurons affected by Chtx (> or = 100 nM). These convergent results support that a Ca(2+)-activated K+ current (IC) contributes to action-potential repolarization in a restricted subpopulation of C-fiber neurons. 3. Tetraethylammonium (TEA; 1-10 mM) increased APD considerably further in the presence of 100-250 nM Chtx or Ibtx, or in nominally Ca(2+)-free superfusate in 14/14 intracellularly recorded C-fiber neurons. TEA affected APD similarly in subpopulations of neurons with and without IC, suggesting that a voltage-dependent K+ current (IK) contributes significantly to action-potential repolarization in most nodose C-fiber neurons. 4. Substitution of Mn2+ for Ca2+ reduced outward whole-cell currents elicited by voltage command steps positive to -30 mV (2-25 ms) in a subpopulation of 21/36 dissociated nodose neurons, supporting the heterogeneous expression of IC. The kinetics of outward tail current relaxations (tau s of 1.5-2 ms) measured at the return of 2-3 ms depolarizing steps to -40 mV were indistinguishable in neurons with and without IC, precluding a separation of the nodose IC and IK by a difference in deactivation rates. 5. Chtx (10-250 nM) reduced in a subpopulation of 3/8 C-fiber neurons the total outward current elicited by voltage steps depolarized to -30 mV in single microelectrode voltage-clamp recordings. TEA (5-10 mM) further reduced outward current in the presence of 100-250 nM Chtx in all eight experiments. The Chtx-sensitive current was taken to represent IC, and the TEA-sensitive current, the IK component contributing to action-potential repolarization. 6. Rapidly inactivating current (IA) was implicated in action-potential repolarization in a subpopulation of intracellularly recorded C-fiber neurons. In 4/7 neurons, incremented hyperpolarizing prepulses negative to -50 mV progressively shortened APD.(ABSTRACT TRUNCATED AT 400 WORDS)


2000 ◽  
Vol 278 (3) ◽  
pp. L485-L491 ◽  
Author(s):  
Radhika Kajekar ◽  
Allen C. Myers

The effect of bradykinin on membrane properties of parasympathetic ganglion neurons in isolated guinea pig bronchial tissue was studied using intracellular recording techniques. Bradykinin (1–100 nM) caused a reversible membrane potential depolarization of ganglion neurons that was not associated with a change in input resistance. The selective bradykinin B2 receptor antagonist HOE-140 inhibited bradykinin-induced membrane depolarizations. Furthermore, the cyclooxygenase inhibitor indomethacin attenuated bradykinin-induced membrane depolarizations to a similar magnitude (∼70%) as HOE-140. However, neurokinin-1 and -3 receptor antagonists did not have similar inhibitory effects. The ability of bradykinin to directly alter active properties of parasympathetic ganglion neurons was also examined. Bradykinin (100 nM) significantly reduced the duration of the afterhyperpolarization (AHP) that followed four consecutive action potentials. The inhibitory effect of bradykinin on the AHP response was reversed by HOE-140 but not by indomethacin. These results indicate that bradykinin can stimulate airway parasympathetic ganglion neurons independent of sensory nerve activation and provide an alternative mechanism for regulating airway parasympathetic tone.


2000 ◽  
Vol 84 (3) ◽  
pp. 1404-1413 ◽  
Author(s):  
Tomoshige Koga ◽  
Robert M. Bradley

The properties of afferent sensory neurons supplying taste receptors on the tongue were examined in vitro. Neurons in the geniculate (GG) and petrosal ganglia (PG) supplying the tongue were fluorescently labeled, acutely dissociated, and then analyzed using patch-clamp recording. Measurement of the dissociated neurons revealed that PG neurons were significantly larger than GG neurons. The active and passive membrane properties of these ganglion neurons were examined and compared with each other. There were significant differences between the properties of neurons in the PG and GG ganglia. The mean membrane time constant, spike threshold, action potential half-width, and action potential decay time of GG neurons was significantly less than those of PG neurons. Neurons in the PG had action potentials that had a fast rise and fall time (sharp action potentials) as well as action potentials with a deflection or hump on the falling phase (humped action potentials), whereas action potentials of GG neurons were all sharp. There were also significant differences in the response of PG and GG neurons to the application of acetylcholine (ACh), serotonin (5HT), substance P (SP), and GABA. Whereas PG neurons responded to ACh, 5HT, SP, and GABA, GG neurons only responded to SP and GABA. In addition, the properties of GG neurons were more homogeneous than those of the PG because all the GG neurons had sharp spikes and when responses to neurotransmitters occurred, either all or most of the neurons responded. These differences between neurons of the GG and PG may relate to the type of receptor innervated. PG ganglion neurons innervate a number of receptor types on the posterior tongue and have more heterogeneous properties, while GG neurons predominantly innervate taste buds and have more homogeneous properties.


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