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PubMed2000

Effects of cervical spinal cord stimulation on cerebral blood flow in the rat.

OBJECT: Spinal cord stimulation (SCS) is frequently used for the treatment of chronic pain. Although the mechanisms by which SCS alleviates pain are unclear, they are believed to involve changes within the dorsal horn of the spinal cord. Spinal cord stimulation has also been found to cause significant vasodilation in the peripheral vasculature. The mechanisms underlying this effect are thought to involve sympathetic blockade. A rostral vasodilatory effect has also been described, but changes in cerebral blood flow (CBF) have been poorly delineated. Using laser Doppler flowmetry (LDF), the authors examined the effects of cervical SCS on CBF in rats. METHODS: Cervical SCS was found to result in a significant increase in cortical LDF values (83 +/- 11% [mean +/- standard error of the mean]). The increase in cortical LDF values was not accompanied by a significant increase in systemic blood pressure. Stimulation of the upper cervical spinal cord was more effective in inducing LDF changes than was that of the lower cervical cord. Changes in SDS-induced LDF values were significantly attenuated after spinal cord transection at the cervicomedullary junction and by the administration of the sympathetic blocker hexamethonium. CONCLUSIONS: These results indicate that cervical SCS may induce cerebral vasodilation and that this effect may involve indirect effects on vasomotor centers in the brainstem as well as an alteration in sympathetic tone.

Analysis of Variance↗
PubMed1995

Effects of Ca2+ channel blockers on directional selectivity of rabbit retinal ganglion cells.

1. Extracellular recordings were made from ON-OFF directionally selective ganglion cells in superfused rabbit retinas in order to examine the effects of voltage-activated Ca2+ channel blockers on the response of these ganglion cells to a moving bar of light. 2. Bath application of Cd2+ (67-110 microM) abolished directional selectivity in the ganglion cells. That is, the cells gave nearly equal responses to the leading and trailing edges of a bar of light moved in the preferred and null directions. This effect of Cd2+ was rapidly reversible. 3. Directional selectivity in the ganglion cells was not affected by Ni2+ (120-440 microM), Co2+ (180-690 microM), or the L-type Ca2+ channel blockers nicardipine (7-29 microM) and methoxyverapamil (18-60 microM). These blockers did, however, reduce the responses of the ganglion cells to a bar of light moved in the preferred direction. 4. omega-Conotoxin MVIIC (130 nM-1.9 microM), which potently blocks N-type and Q-type Ca2+ channels, abolished directional selectivity in the ganglion cells. omega-Conotoxin MVIIC not only brought out large leading and trailing edge responses to movement of a bar of light in the null direction, but it also increased the leading and trailing edge responses to movement of the bar of light in the preferred direction. The effect of omega-conotoxin MVIIC was slowly reversible. 5. The N-type Ca2+ channel blocker omega-conotoxin GVIA (1.4-6.3 microM) did not abolish directional selectivity in the ganglion cells. This blocker did, however, bring out some response to the leading edge of a bar of a light moved in the null direction. This effect of omega-conotoxin GVIA appeared to be irreversible. 6. omega-Agatoxin IVA, a potent blocker of P-type Ca2+ channels, when bath applied at low concentrations (66-83 nM), increased the responses to movement of a bar of light in the preferred direction but brought out only small responses to movement of the bar of light in the null direction. At high concentrations (250-280 nM) that reportedly block Q-type Ca2+ channels by > or = 50%, omega-agatoxin IVA nearly abolished directional selectivity. This effect of omega-agatoxin IVA was slowly reversible. 7. These results indicate that omega-conotoxin MVIIC- and omega-agatoxin IVA-sensitive Ca2+ channels (possibly Q-type channels) play an important role in the generation of directional selectivity in rabbit retinal ganglion cells.

Action Potentials↗
PubMed1965

Physiological and pharmacological interactions of antihypertensive drugs.

The complex mechanisms that maintain the blood pressure can be interfered with at many points by drugs. A drug acting at one point may be potentiated by another which blocks a compensatory reflex minimizing the effect of the first. Many therapeutically useful drug combinations have a nonspecific mechanism of this kind although drugs that act upon different points in the sympathetic efferent vasomotor pathway have not been proved to have a useful additive effect.It is not easy to prove a synergistic action of two drugs unless it is large. The best supported examples are combinations of either a diuretic or a vasodilator with a sympathetic blocking drug. These combinations are the ones most widely used in treatment of hypertension. They allow the dose of each active substance to be reduced so that unwanted side-effects are decreased without losing the desired action on the blood pressure.Drug combinations have special risks besides their obvious advantages. Patients are more likely to become confused and take the wrong doses if their treatment regime is complicated. Two drugs which are individually nontoxic may have dangers when used together. Oliguria and a mounting blood urea may follow combined use of powerful modern diuretics. Toxic effects may be entirely unrelated to the main therapeutic action of the drug, as with the enhanced diabetogenic effect of diazoxide used with hydrochlorothiazide.Several potent cardiovascular drugs modify the response to drugs which might be given to raise the blood pressure in an emergency. No drug in common therapeutic use seriously reduces the response to injected noradrenaline but some, such as sympathetic blockers and monoamine oxidase inhibitors, greatly increase sensitivity. Pressor amines that act indirectly by noradrenaline release may be ineffective in the presence of drugs which deplete or insulate the stores of the transmitter in adrenergic nerve endings.The advantages and disadvantages of drug interactions deserve more thought and study than they usually receive.

Antihypertensive Agents↗
PubMed1991

Effect of (+)-sparteine on nicotinic acetylcholine receptors in the neurons of rat superior cervical ganglion.

The effects of (+)-sparteine, a ganglionic blocking agent, on acetylcholine (ACh)-induced membrane currents and on fast excitatory postsynaptic currents (EPSCs) were studied in the neurons of rat isolated superior cervical ganglion, with the whole-cell patch-clamp recording method and the two-electrode voltage-clamp method, respectively. (+)-Sparteine (2 microM) reduced the ACh-induced current caused by activation of nicotinic ACh receptors (AChRs) in a voltage-independent manner at membrane potentials of -50 mV to +30 mV, whereas its blocking effect increased at more negative membrane potentials. The dose-response relationship for ACh was modified by 2 microM (+)-sparteine at -50 mV and at -90 mV in a fashion typical for competitive rather than noncompetitive antagonists. The apparent mean open time of the AChR channel, as estimated from the power density spectrum of the ACh-induced current fluctuations at -90 mV, was not decreased by 2 microM (+)-sparteine, in contrast to what was observed with hexamethonium, the well known open-channel blocker for ganglionic AChRs. At higher concentrations, i.e., 5 microM and 10 microM (lower concentrations were not effective), (+)-sparteine reduced the amplitude of the EPSC and the time constant of the EPSC decay. The former effect was voltage independent, whereas the latter effect was voltage independent at membrane potentials of -70 mV and more positive and increased at membrane potentials of -90 and -110 mV. These results suggest that (+)-sparteine produces in ganglionic AChRs a competitive blocking effect and, in addition, an open-channel blockade. The latter component probably provides a smaller contribution than does the former to the blockade by (+)-sparteine of the ACh-induced current. Conformational analysis of the (+)-sparteine molecule was performed, and the dimensions of the molecule were measured. Minimum dimensions of the space-filling profile for two conformers, high and low populated, were found to be 7.3 x 7.9 A and 6.8 x 7.5 A, respectively. Both profiles are larger than the channel profile at which the open-channel blockers have been suggested to bind, which may explain comparatively low open-channel-blocking activity of (+)-sparteine.

Acetylcholine↗
PubMed2001

Effects of autonomic blockers on linear and nonlinear indexes of blood pressure and heart rate in SHR.

Recent results in normotensive Wistar-Kyoto (WKY) rats show that nonlinear method may be more specific to quantify sympathetic and parasympathetic activities than the low (LF) and high frequencies (HF) spectral powers of blood pressure (BP) and R-R interval (RR). The present study extends this conclusion to spontaneously hypertensive rats (SHR). Blood pressure was recorded for 30 min before and after intravenous injection of saline, hexamethonium, atropine, atenolol, or prazosin. Mean level, standard deviation (SD), spectral LF and HF components, and three nonlinear indexes (percentage of recurrence, percentage of determinism, and length index of the recurrence plot method) were used to analyze the BP and RR signals. In conscious SHR, sympathetic but not parasympathetic blockade reduced BP level and LF-BP, and increased nonlinear indexes of BP. RR increased after beta-sympathetic and ganglionic blockade, decreased after parasympathetic blockade, and remained unchanged after alpha(1)-sympathetic blockade. SD-RR decreased after ganglionic and alpha(1) blockade, whereas HF-RR increased after beta-sympathetic blockade. The effects on nonlinear indexes of RR are clear and consistent: only alpha(1)-blockade increased the indexes. Our nonlinear indexes may be useful to investigate cardiovascular functions in normotension and hypertension.

Adrenergic alpha-Antagonists↗
PubMedDate not supplied

[Drug-induced respiratory disorders].

Drugs induced respiratory disorders include bronchospasm, extrinsic alveolitis, and diffuse interstitial pulmonary fibrosis. Bronchospasm may be due to the action of pharmacodynamic agents on autonomic control of bronchial tone (beta-blockers, beta-agonists...) or to a hypersensitivity reaction (penicillins, sulfonamides, anti-inflammatory compounds...). Extrinsic alveolitis usually follows administration of anti-infective medication but other drugs may be implicated. Prolonged use of a wide variety of drugs, particularly cytotoxic agents, is necessary to provoke the onset of a diffuse interstitial pulmonary fibrosis.

Adrenergic alpha-Agonists↗
PubMed1996

Otilonium: a potent blocker of neuronal nicotinic ACh receptors in bovine chromaffin cells.

1. Otilonium, a clinically useful spasmolytic, behaves as a potent blocker of neuronal nicotinic acetylcholine receptors (AChR) as well as a mild wide-spectrum Ca2+ channel blocker in bovine adrenal chromaffin cells. 2. 45Ca2+ uptake into chromaffin cells stimulated with high K+ (70 mM, 1 min) was blocked by otilonium with an IC50 of 7.6 microM. The drug inhibited the 45Ca2+ uptake stimulated by the nicotinic AChR agonist, dimethylphenylpiperazinium (DMPP) with a 79 fold higher potency (IC50 = 0.096 microM). 3. Whole-cell Ba2+ currents (IBa) through Ca2+ channels of voltage-clamped chromaffin cells were blocked by otilonium with an IC50 of 6.4 microM, very close to that of K(+)-evoked 45Ca2+ uptake. Blockade developed in 10-20 s, almost as a single step and was rapidly and almost fully reversible. 4. Whole-cell nicotinic AChR-mediated currents (250 ms pulses of 100 microM DMPP) applied at 30 s intervals were blocked by otilonium in a concentration-dependent manner, showing an IC50 of 0.36 microM. Blockade was induced in a step-wise manner. Wash out of otilonium allowed a slow recovery of the current, also in discrete steps. 5. In experiments with recordings in the same cells of whole-cell IDMPP, Na+ currents (INa) and Ca2+ currents (ICa), 1 microM otilonium blocked 87% IDMPP, 7% INa and 13% ICa. 6. Otilonium inhibited the K(+)-evoked catecholamine secretory response of superfused bovine chromaffin cells with an IC50 of 10 microM, very close to the IC50 for blockade of K(+)-induced 45Ca2+ uptake and IBa. 7. Otilonium inhibited the secretory responses induced by 10 s pulses of 50 microM DMPP with an IC50 of 7.4 nM. Hexamethonium blocked the DMPP-evoked responses with an IC50 of 29.8 microM, 4,000 fold higher than that of otilonium. 8. In conclusion, otilonium is a potent blocker of nicotinic AChR-mediated responses. The drugs also blocked various subtypes of neuronal voltage-dependent Ca2+ channels at a considerably lower potency. Na+ channels were unaffected by otilonium. This extraordinary potency of otilonium in blocking nicotinic AChR, unrecognised until now, might account in part for its well known spasmolytic effects.

Animals↗
PubMed1982

Psychiatric side effects of antihypertensive drugs other than reserpine.

The psychiatric side effects of the major antihypertensive drugs other than reserpine are reviewed, including centrally acting drugs such as methyldopa and clonidine, peripheral adrenergic drugs such as guanethidine, beta-adrenoceptor blockers such as propranolol, and diuretics. Problems with differential diagnosis and with the interpretation of case reports make assessment of psychiatric side effects difficult. Sedation and sleep disturbances are the most common side effects, occurring with methyldopa, clonidine, and propranolol. Only methyldopa is clearly associated with depression. Other reported effects are toxic confusional states and psychotic reactions. These are rare, however, and no clear patterns of development have been recognized.

Adrenergic beta-Antagonists↗
PubMedDate not supplied

[A comparative study of the central H-cholinergic-blocking and NMDA-blocking actions of MK-801, memantin, amantadine, pyrilen and IEM-1754 in experiments on intact rats].

Pyrilene acts as a central H-cholinoblocker upon intramuscular injection at a dose of 0.02-0.08 mg/kg, and as an NMDA-blocker, when the dose is increased to 0.2-0.8 mg/kg. Similarly, amantadine exhibits the properties of H-cholinoblocker and NMDA-blocker in the dose intervals 10-15 mg/kg and 120-180 mg/kg, respectively. The activity of MK-801 markedly exceeds that of memantine, although close doses of both NMDA-blockers inhibit the NMDA and corazole effects, as well as the central effects (analgesia and seizure) of nicotine, thus showing no significant selectivity with respect to NMDA. IEM-1754 tested on intact animals exhibited a selective action upon the NMDA receptors, preventing the NMDA-induced analgesia and lethality and the corazole-induced convulsions at doses 10-100 times lower as compared to those preventing nicotine-induced seizure and analgesia.

Adamantane↗
PubMed2006

Increased cholinergic contractions of jejunal smooth muscle caused by a high cholesterol diet are prevented by the 5-HT4 agonist--tegaserod.

BACKGROUND: Excess cholesterol in bile and in blood is a major risk factor for the respective development of gallbladder disease and atherosclerosis. This lipid in excess negatively impacts the functioning of other smooth muscles, including the intestine. Serotonin is an important mediator of the contractile responses of the small intestine. Drugs targeting the serotonin receptor are used as prokinetic agents to manage intestinal motor disorders, in particular irritable bowel syndrome. Thus, tegaserod, acting on 5-HT4 receptor, ideally should obviate detrimental effects of excessive cholesterol on gastrointestinal smooth muscle. In this study we examined the effect of tegaserod on cholesterol-induced changes in the contractile responses of intestinal smooth muscle. METHODS: The effects of a high cholesterol (1%) diet on the in vitro contractile responses of jejunal longitudinal smooth muscle from Richardson ground squirrels to the cholinergic agonist carbachol were examined in the presence or absence of tetrodrodotoxin (TTX). Two groups of animals, fed either low (0.03%) or high cholesterol rat chow diet, were further divided into two subgroups and treated for 28 days with either vehicle or tegaserod. RESULTS: The high cholesterol diet increased, by nearly 2-fold, contractions of the jejunal longitudinal smooth muscle elicited by carbachol. These cholinergic contractions were mediated by muscarinic receptors since they were blocked by scopolamine, a muscarinic receptor antagonist, but not by the nicotinic receptor antagonist, hexamethonium. Tegaserod treatment, which did not affect cholinergic contractions of tissues from low cholesterol fed animals, abrogated the increase caused by the high cholesterol diet. With low cholesterol diet TTX enhanced carbachol-evoked contractions, whereas this action potential blocker did not affect the augmented cholinergic contractions seen with tissues from animals on the high cholesterol diet. Tegaserod-treatment removed the effects of a high cholesterol diet on neuronal muscarinic receptors, as the potentiating effect of TTX on carbachol-elicited contractions was maintained in these animals. CONCLUSION: A high cholesterol diet causes significant changes to cholinergic neurotransmission in the enteric nerves of the jejunum. The mechanisms by which these effects of cholesterol are reversed by tegaserod are unknown, but relate to removal of an inhibitory effect of cholesterol on enteric nerves.

Action Potentials↗
PubMed2003

Sympathetic mechanisms in cerebral blood flow alterations induced by spinal cord stimulation.

OBJECT: Cervical spinal cord stimulation (SCS) has been found to augment cerebral blood flow (CBF) in a number of animal models, although the mechanisms underlying the cerebrovascular effects of SCS are poorly described. In this study, the authors examined the role of sympathetic tone in CBF alterations induced by SCS in rats. METHODS: Spinal cord stimulation was performed at three intervals while CBF was monitored with laser Doppler flowmetry (LDF). Either hexamethonium (5, 10, or 20 mg/kg), prazosin (0.25, 0.5, or 1 mg/kg), idazoxan (0.5, 1, or 2 mg/kg), propranolol (1, 2, or 4 mg/kg), or vehicle was administered intravenously before the second stimulation. Changes in LDF values due to SCS were recorded as the percentage of change from baseline values and were analyzed. In vehicle-treated animals, SCS increased LDF values by 60.5 +/- 1.8% over baseline, whereas both high-dose hexamethonium and prazosin completely abolished the SCS-induced increases in LDF values. On the other hand, LDF values increased by 50.9 +/- 4% and 61.4 +/- 4% after SCS in the presence of idazoxan or propranolol, respectively. Administration of sympathetic nervous system blockers resulted in a variable degree of systemic hypotension as well. Nevertheless, induced hypotension without sympathetic blockade had only a minimal effect on SCS-induced augmentation of LDF values (48 +/- 1.4% over baseline). CONCLUSIONS: Sympathetic tone plays a major role in SCS-induced increases in CBF. This effect seems to be mediated primarily by alpha1-adrenergic receptors. Systemic hypotension alone cannot explain the effects of sympathetic blockade on the SCS response. Clinical use of SCS in the treatment of cerebral ischemia should take alpha1-adrenergic receptor sympathetic tone into account.

Adrenergic alpha-Antagonists↗
PubMed1990

Ca2(+)-evoked [3H]dopamine release from synaptosomes is dependent on neuronal type Ca2+ channels and is not mediated by acetylcholine, glutamate or aspartate release.

Elevation of potassium concentrations ([K+]) in the presence of Ca2+ is the most common method of evoking neurotransmitter release from synaptosomes. However, we have been investigating a method of releasing dopamine from synaptosomes that does not involve using elevated [K+]. In this paradigm of neurotransmitter release, dopamine is released from synaptosomes, previously exposed to micromolar or lower [Ca2+], by 1.25 mM Ca2+ in the presence of non-depolarizing [K+] (4.5 mM). The present experiments characterize the Ca2+ channel(s) involved in the Ca2(+)-evoked release of dopamine from synaptosomes, and determine whether the release is mediated by acetylcholine, glutamate or aspartate. omega-Conotoxin (10 nM), which blocks N-, L- and possibly T-type voltage-sensitive Ca2+ channels (VSCC), inhibited the Ca2(+)-evoked [3H]dopamine release from either striatal or olfactory tubercle synaptosomes to less than 50% of control. Neither 1 microM nifedipine nor 1 microM verapamil, which block L-type VSCC, affected Ca2(+)-evoked release. The N- and T-type VSCC blocker neomycin and the nonspecific Ca2+ antagonist, cobalt2+, inhibited release to a greater extent than omega-conotoxin. At 1 mM, both compounds inhibited release to approximately 30% of control. Neither the excitatory neurotransmitter glutamate nor aspartate (2mM) affected 1 microM LY-171555 (a dopamine D2 agonist) inhibition of Ca2(+)-evoked [3H]dopamine release. Also, the glutamate antagonist, glutamic acid diethyl ester, did not affect either Ca2(+)-evoked release or 1 microM LY-171555 inhibition thereof. The nicotinic antagonist hexamethonium (10 microM) and the muscarinic antagonist atropine (1 microM) were also ineffective in inhibiting Ca2(+)-evoked release or LY-171555 inhibition of release.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗
PubMed2003

Fast synaptic connections from CBIs to pattern-generating neurons in Aplysia: initiation and modification of motor programs.

Consummatory feeding movements in Aplysia californica are organized by a central pattern generator (CPG) in the buccal ganglia. Buccal motor programs similar to those organized by the CPG are also initiated and controlled by the cerebro-buccal interneurons (CBIs), interneurons projecting from the cerebral to the buccal ganglia. To examine the mechanisms by which CBIs affect buccal motor programs, we have explored systematically the synaptic connections from three of the CBIs (CBI-1, CBI-2, CBI-3) to key buccal ganglia CPG neurons (B31/B32, B34, and B63). The CBIs were found to produce monosynaptic excitatory postsynaptic potentials (EPSPs) with both fast and slow components. In this report, we have characterized only the fast component. CBI-2 monosynaptically excites neurons B31/B32, B34, and B63, all of which can initiate motor programs when they are sufficiently stimulated. However, the ability of CBI-2 to initiate a program stems primarily from the excitation of B63. In B31/B32, the size of the EPSPs was relatively small and the threshold for excitation was very high. In addition, preventing firing in either B34 or B63 showed that only a block in B63 firing prevented CBI-2 from initiating programs in response to a brief stimulus. The connections from CBI-2 to the buccal ganglia neurons showed a prominent facilitation. The facilitation contributed to the ability of CBI-2 to initiate a BMP and also led to a change in the form of the BMP. The cholinergic blocker hexamethonium blocked the fast EPSPs induced by CBI-2 in buccal ganglia neurons and also blocked the EPSPs between a number of key CPG neurons within the buccal ganglia. CBI-2 and B63 were able to initiate motor patterns in hexamethonium, although the form of a motor pattern was changed, indicating that non-hexamethonium-sensitive receptors contribute to the ability of these cells to initiate bursts. By contrast to CBI-2, CBI-1 excited B63 but inhibited B34. CBI-3 excited B34 and not B63. The data indicate that CBI-1, -2, and -3 are components of a system that initiates and selects between buccal motor programs. Their behavioral function is likely to depend on which combination of CBIs and CPG elements are activated.

Action Potentials↗
PubMed1977

Action of histamine and H1 and H2 blockers on the cardiopulmonary circulation.

Systemic and pulmonary hemodynamic responses to histamine were investigated inchronically instrumented unanesthetized nonpregnant ewes. Histamine was administered intravenously and into the pulmonary artery. The effects of the same doses of histamine were assessed following H1 and H2 receptor blockade. The effects ocular changes were also monitored. Results indicate that intravenous histamine produces tachycardia, systemic hypotension, pulmonary hypertension, and reduced cardiac output. The pulmonary response could be modified significantly by pentobarbital anesthesia. When injected directly into the pulmonary artery histamine failed to elicit any circulatory response. Blockade of H1 and H2 receptors, as well as autonomic ganglia, resulted in a comparable attentuation of the histamine circulatory response. It is concluded that a) central hemodynamic responses do not seem to be mediated through specific H1 and H2 receptors; b) histamine-induced pulmonary vasoconstriction can be reversed by pentobarbital anesthesia, and c) the absence of circulatory response to intrapulmonary histamine administration suggests that whatever receptors that may exist in the pulmonary vascular bed are not necessary for the central hemodynamic effects.

Animals↗
PubMed1997

Synapse formation and hypoxic signalling in co-cultures of rat petrosal neurones and carotid body type 1 cells.

1. To investigate synaptic mechanisms mediating chemosensory signalling in the carotid body, we developed co-cultures of chemoreceptor type 1 cell clusters and dissociated petrosal neurones (PNs) from 7- to 14-day-old rat pups and tested for functional connectivity in CO2-HCO3(-)-or Hepes-buffered medium at approximately 35 degrees C. 2. When cultured without type 1 cells, PNs were almost always quiescent (n = 104) and unresponsive to hypoxia (Po2 = 5-25 mmHg) during perforated patch, whole-cell recordings of membrane potential or voltage-activated currents; in contrast, many PNs (77 out of 170) that were juxtaposed to type 1 cell clusters in co-culture displayed spontaneous activity, comprising spikes and subthreshold potentials (SSPs) that resembled synaptic potentials. 3. Additional tests suggested that de novo chemical synapses developed between PNs and type 1 cell clusters in vitro. For example: (i) the spontaneous activity was reversibly suppressed by substituting low calcium-high magnesium in the bath; (ii) SSPs had variable amplitudes and persisted following action potential blockade with TTX (1 microM); (iii) the interval distribution between successive spontaneous events appeared random; and (iv) the frequency of spontaneous potentials was diminished (reversibly) by the nicotinic antagonist hexamethonium (100 microM), suggesting contributions from the spontaneous release of ACh. 4. Many complexes of 'juxtaposed' PNs and type 1 clusters were physiologically functional, since exposure to hypoxia caused a reversible depolarization and/or increased spike discharge in approximately 30% of such neurones (n = 140). The hypoxia-induced spike discharge persisted in the presence of the dopamine D2 receptor blocker spiperone (10-50 microM; n = 5); however, this discharge was reversibly inhibited by 100-200 microM hexamethonium, suggesting that it was mediated, at least in part, by ACh acting through nicotinic receptors. 5. The hypoxia-induced spike discharge and frequency of spontaneous potentials in co-cultured PNs were reversibly suppressed when the buffer was switched from CO2-HCO3- to Hepes (10 mM) at pH 7.4; further, 'functional' PNs that displayed spontaneous activity and/or hypoxia-induced responses in co-culture were encountered more frequently in CO2-HCO3- (> or = 40%) than in Hepes (< or = 26%) buffer. 6. We conclude that functional chemical synapses can develop de novo in cultures of carotid body type 1 cells and PNs and that ACh is probably an important excitatory neurotransmitter secreted from type 1 cells during hypoxic chemotransduction in the rat carotid body.

Acetylcholine↗