Presynaptic K-channel blockade counteracts the depressant effect of adenosine in olfactory cortex

Scholfield, C.N.; Steel, Linda K.

doi:10.1016/0306-4522(88)90313-2

Cited by 30 publications

(12 citation statements)

References 39 publications

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“…In addition, it has been shown that 4-AP does not block the effects of adenosine on Ca2+ fluxes in the CA1 area of rat hippocampus (Schubert and Heinemann, 1988). By contrast, blockade of presynaptic potassium channels by, e.g., 4-AP, in the rat olfactory cortex does block the effects of adenosine (Scholfield and Steel, 1988). The present negative finding does not exclude that stimulation of a potassium conductance is the mechanism by which adenosine blocks ACh release in the rat hippocampus.…”

Section: Discussioncontrasting

confidence: 68%

Differential Sensitivity to Blockade by 4‐Aminopyridine of Presynaptic Receptors Regulating [³H]Acetylcholine Release from Rat Hippocampus

Fredholm

1990

Journal of Neurochemistry

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The inhibitory effect of an adenosine analogue, R-N6-phenylisopropyl adenosine (R-PIA), of the cholinergic agonist carbachol, and of morphine on 3H efflux from [3H]choline-labeled field-stimulated rat hippocampal slices was compared with that produced by two inhibitors of N- and L-type Ca2+ channels, omega-conotoxin (CgTx; conotoxin GVIA) and cadmium chloride. 4-Aminopyridine (4-AP) caused a dose-dependent increase in evoked transmitter release, with a maximal effect (an almost threefold increase) at 100 microM. 4-AP (100 microM) did not affect the actions of CgTx, cadmium chloride, and R-PIA but almost abolished the effect of carbachol and morphine. The present results indicate that presynaptic muscarinic and opiate receptors reduce acetylcholine release by a mechanism that is somewhat different from that used by adenosine A1 receptors. Furthermore, the results indicate that presynaptic A1 receptors on hippocampal cholinergic neurons do not primarily regulate 4-AP-dependent potassium channels, but that they might act directly on a Ca2+ conductance.

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Section: Discussioncontrasting

confidence: 68%

Differential Sensitivity to Blockade by 4‐Aminopyridine of Presynaptic Receptors Regulating [³H]Acetylcholine Release from Rat Hippocampus

Fredholm

1990

Journal of Neurochemistry

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“…The action of 4-AP suggests, at first glance, that the three compounds cause presynaptic inhibition by increasing a K+ conductance at the presynaptic terminal, as has been hypothesized for the action of adenosine in guinea-pig olfactory cortex (Scholfield & Steel, 1988). However, the effects of the low-Ca2+/4-AP treatment on NPY and baclofen responses are not consistent with an increase in K+ conductance.…”

Section: Resultsmentioning

confidence: 93%

“…Nearly all of these substances have been shown to inhibit calcium influx into cultured or acutely dissociated neurones (Dolphin & Scott, 1986;Macdonald et al, 1986;Wanke et al, 1987;Walker et al, 1988), and most are known to activate potassium conductances in cell bodies (Newberry & Nicoll, 1984;Egan & North, 1986;Greene & Haas, 1985;Zidichouski et al, 1990 aminopyridine (4-AP), which blocks potassium conductances at presynaptic terminals (Buckle & Haas, 1982). 4-AP at concentrations well below those needed to affect the somatic 'A' current has been shown to block the presynaptic actions of NPY in hippocampal CAl (Colmers et al, 1988); higher concentrations block presynaptic inhibition mediated by adenosine in guinea-pig olfactory cortex (Scholfield & Steel, 1988). Lowering extracellular calcium concentrations in the presence of 4-AP restored NPY-induced inhibition, suggesting the inhibition of a presynaptic terminal calcium conductance by NPY (Colmers et al, 1988).…”

Section: Introductionmentioning

confidence: 99%

“…aminopyridine (4-AP), which blocks potassium conductances at presynaptic terminals (Buckle & Haas, 1982). 4-AP at concentrations well below those needed to affect the somatic 'A' current has been shown to block the presynaptic actions of NPY in hippocampal CAl (Colmers et al, 1988); higher concentrations block presynaptic inhibition mediated by adenosine in guinea-pig olfactory cortex (Scholfield & Steel, 1988). Lowering extracellular calcium concentrations in the presence of 4-AP restored NPY-induced inhibition, suggesting the inhibition of a presynaptic terminal calcium conductance by NPY (Colmers et al, 1988).…”

Section: Introductionmentioning

confidence: 99%

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4‐Aminopyridine and low Ca²⁺ differentiate presynaptic inhibition mediated by neuropeptide Y, baclofen and 2‐chloroadenosine in rat hippocampal CA1 in vitro

Klapstein

Colmers

1992

British J Pharmacology

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1 Presynaptic inhibition is mediated by several receptors at the stratum radiatum-CA1 synapse of rat hippocampus. We tested whether the same mechanism is activated by neuropeptide Y (NPY), baclofen and 2-chloroadenosine (2-CA), reasoning that if the receptors all activated the same process, then they should all respond to indirect manipulations of transmitter release in the same manner. 2 The effects on presynaptic inhibition by the potassium channel blocker, 4-aminopyridine (4-AP) and low extracellular concentrations of Ca2 + in the presence of 4-AP were compared using evoked population excitatory postsynaptic potentials (p.e.p.s.p.) responses in the rat hippocampal slice in vitro. 3 Log concentration-effect relationships for the inhibition of excitatory transmission were constructed for all 3 drugs in normal saline, and in the presence of 30 and 100,M 4-AP. 4-AP reduced the inhibition mediated by all three substances, 100pM 4-AP was only slightly more effective than 30 JM.4 Lowering extracellular Ca2+ from 1.5 to 0.75mM in the presence of 30,uM 4-AP restored the presynaptic inhibition caused by all effective concentrations of NPY and baclofen. By contrast, inhibition caused by 2-CA was not restored by lowering Ca2+, except at concentrations of 2-CA greater than 10pUM. 5 The results are consistent with the hypothesis that presynaptic NPY Y2 and GABAB receptors both inhibit transmitter release by the inhibition of voltage-dependent Ca2+ influx, but that the A1 adenosine receptor may activate a different presynaptic mechanism.

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“…For example, in vitro reports have described direct effects of ketones on K + channels and vesicular neurotransmitter uptake sites, 22,29 and low glucose can inhibit synaptic transmission 3 via activation of adenosine A 1 receptors and K + channels. 23,48 …”

Section: Introductionmentioning

confidence: 99%

Ketogenic Diets and Thermal Pain: Dissociation of Hypoalgesia, Elevated Ketones, and Lowered Glucose in Rats

Ruskin

Suter

Ross

et al. 2013

The Journal of Pain

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Ketogenic diets are high-fat, low-carbohydrate formulations effective in treating medically-refractory epilepsy, and recently we demonstrated lowered sensitivity to thermal pain in rats fed a ketogenic diet for 3–4 weeks. Regarding anticonvulsant and hypoalgesic mechanisms, theories are divided as to direct effects of increased ketones and/or decreased glucose, metabolic hallmarks of these diets. To address this point, we characterized the time course of ketogenic diet-induced thermal hypoalgesia, ketosis, and lowered glucose in young male rats fed ad libitum on normal chow or ketogenic diets. A strict 6.6:1 (fat:(carbohydrates + protein), by weight), ketogenic diet increased blood ketones and reduced blood glucose by two days of feeding, but thermal hypoalgesia did not appear until 10 days. Thus, ketosis and decreased glucose are not sufficient for hypoalgesia. After feeding a 6.6:1 ketogenic diet for 19 days, decreased thermal pain sensitivity and changes in blood chemistry reversed one day after return to normal chow. Effects on were consistent between two different diet formulations: a more moderate and clinically-relevant ketogenic diet formula (3.0:1) produced hypoalgesia and similar changes in blood chemistry as the 6.6:1 diet, thus increasing translational potential. Furthermore, feeding the 3.0:1 diet throughout an extended protocol (10–11 weeks) revealed that significant hypoalgesia and increased ketones persisted whereas low glucose did not, demonstrating that ketogenic diet-induced hypoalgesia does not depend on reduced glucose. In separate experiments we determined that effects on thermal pain responses were not secondary to motor or cognitive changes. Together, these findings dissociate diet-related changes in nociception from direct actions of elevated ketones or decreased glucose, and suggest mechanisms with a slower onset in this paradigm. Overall, our data indicate that metabolic approaches can relieve pain.

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Presynaptic K-channel blockade counteracts the depressant effect of adenosine in olfactory cortex

Cited by 30 publications

References 39 publications

Differential Sensitivity to Blockade by 4‐Aminopyridine of Presynaptic Receptors Regulating [³H]Acetylcholine Release from Rat Hippocampus

Differential Sensitivity to Blockade by 4‐Aminopyridine of Presynaptic Receptors Regulating [³H]Acetylcholine Release from Rat Hippocampus

4‐Aminopyridine and low Ca²⁺ differentiate presynaptic inhibition mediated by neuropeptide Y, baclofen and 2‐chloroadenosine in rat hippocampal CA1 in vitro

Ketogenic Diets and Thermal Pain: Dissociation of Hypoalgesia, Elevated Ketones, and Lowered Glucose in Rats

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Presynaptic K-channel blockade counteracts the depressant effect of adenosine in olfactory cortex

Cited by 30 publications

References 39 publications

Differential Sensitivity to Blockade by 4‐Aminopyridine of Presynaptic Receptors Regulating [3H]Acetylcholine Release from Rat Hippocampus

Differential Sensitivity to Blockade by 4‐Aminopyridine of Presynaptic Receptors Regulating [3H]Acetylcholine Release from Rat Hippocampus

4‐Aminopyridine and low Ca2+ differentiate presynaptic inhibition mediated by neuropeptide Y, baclofen and 2‐chloroadenosine in rat hippocampal CA1 in vitro

Ketogenic Diets and Thermal Pain: Dissociation of Hypoalgesia, Elevated Ketones, and Lowered Glucose in Rats

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Differential Sensitivity to Blockade by 4‐Aminopyridine of Presynaptic Receptors Regulating [³H]Acetylcholine Release from Rat Hippocampus

Differential Sensitivity to Blockade by 4‐Aminopyridine of Presynaptic Receptors Regulating [³H]Acetylcholine Release from Rat Hippocampus

4‐Aminopyridine and low Ca²⁺ differentiate presynaptic inhibition mediated by neuropeptide Y, baclofen and 2‐chloroadenosine in rat hippocampal CA1 in vitro