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PubMed1985

The aminoglycoside antibiotic, gentamicin, fails to block increases in miniature endplate potential frequency induced by the sulfhydryl reagent, N-ethylmaleimide, in low calcium solutions.

N-ethylmaleimide (NEM) increases the frequency of miniature endplate potentials (MEPPs) at the adult rat hemidiaphragm. This sulfhydryl-alkylating agent produces comparable effects in the absence of added calcium (2 mM EGTA), suggesting that the drug releases calcium from internal stores, or promotes calcium-independent release by depolarizing the nerve terminal or interacting more directly with the release mechanism. These increases in frequency are not blocked by the aminoglycoside antibiotic, gentamicin; although the latter agent reduces quantal content and the elevations in MEPP frequency induced by high potassium solutions. The results suggest that gentamicin and NEM act at different sites at the presynaptic terminal, and that the aminoglycosides block voltage-dependent presynaptic calcium influx.

Action Potentials↗
PubMed2001

Direct binding and functional coupling of alpha-synuclein to the dopamine transporters accelerate dopamine-induced apoptosis.

Mutations in alpha-synuclein, a protein highly enriched in presynaptic terminals, have been implicated in the expression of familial forms of Parkinson's disease (PD) whereas native alpha-synuclein is a major component of intraneuronal inclusion bodies characteristic of PD and other neurodegenerative disorders. Although overexpression of human alpha-synuclein induces dopaminergic nerve terminal degeneration, the molecular mechanism by which alpha-synuclein contributes to the degeneration of these pathways remains enigmatic. We report here that alpha-synuclein complexes with the presynaptic human dopamine transporter (hDAT) in both neurons and cotransfected cells through the direct binding of the non-A beta amyloid component of alpha-synuclein to the carboxyl-terminal tail of the hDAT. alpha-Synuclein--hDAT complex formation facilitates the membrane clustering of the DAT, thereby accelerating cellular dopamine uptake and dopamine-induced cellular apoptosis. Since the selective vulnerability of dopaminergic neurons in PD has been ascribed in part to oxidative stress as a result of the cellular overaccumulation of dopamine or dopamine-like molecules by the presynaptic DAT, these data provide mechanistic insight into the mode by which the activity of these two proteins may give rise to this process.

Apoptosis↗
PubMed1977

[Quantitative characteristics of ultrastructural changes in axo-dendritic synapses under the influence of tetanus toxin].

Changes in synaptic ultrastructure of the external geniculate body (EGB) were investigated in rats when a generator of pathologically intensified excitation (GPIE) was produced in this nucleus under the influence of tetanus toxin (TT). At the period of pronounced convulsive activity (24 h after TT injection), synaptic changes were estimated electronmicroscopically and with quantitative comparison of the materials from three groups. The first group included EGB synapses where TT was injected, the second group included contralateral EGB synapses and the third included EGB from the rats injected with inactivated toxin. By means of electron optic computer "Klassimat" average amount of round, flat, anomalous and adjacent to the presynaptic membrane vesicles was measured, average relative length of the active zone, average area of the presynaptic terminal, average relative section areas of pre- and postsynaptic cytoplasm condensation were estimated. In the area of GPIE formation, under the influence of TT, the increased amount of the vesicles related to the presynaptic membrane and that of flat vesicles were statistically significant. At the same time, the synaptic terminals, by the number of vesicles, have bimodal, while the control groups have unimodal distribution.

Animals↗
PubMed2006

Distribution of plasma membrane-associated syntaxins 1 through 4 indicates distinct trafficking functions in the synaptic layers of the mouse retina.

BACKGROUND: Syntaxins 1 through 4 are SNAP receptor (SNARE) proteins that mediate vesicular trafficking to the plasma membrane. In retina, syntaxins 1 and 3 are expressed at conventional and ribbon synapses, respectively, suggesting that synaptic trafficking functions differ among syntaxin isoforms. To better understand syntaxins in synaptic signaling and trafficking, we further examined the cell- and synapse-specific expression of syntaxins 1 through 4 in the mouse retina by immunolabeling and confocal microscopy. RESULTS: Each isoform was expressed in the retina and showed a unique distribution in the synaptic layers of the retina, with little or no colocalization of isoforms. Syntaxin 1 was present in amacrine cell bodies and processes and conventional presynaptic terminals in the inner plexiform layer (IPL). Syntaxin 2 was present in amacrine cells and their processes in the IPL, but showed little colocalization with syntaxin 1 or other presynaptic markers. Syntaxin 3 was found in glutamatergic photoreceptor and bipolar cell ribbon synapses, but was absent from putative conventional glutamatergic amacrine cell synapses. Syntaxin 4 was localized to horizontal cell processes in the ribbon synaptic complexes of photoreceptor terminals and in puncta in the IPL that contacted dopaminergic and CD15-positive amacrine cells. Syntaxins 2 and 4 often were apposed to synaptic active zones labeled for bassoon. CONCLUSION: These results indicate that each syntaxin isoform has unique, non-redundant functions in synaptic signaling and trafficking. Syntaxins 1 and 3 mediate presynaptic transmitter release from conventional and ribbon synapses, respectively. Syntaxins 2 and 4 are not presynaptic and likely mediate post-synaptic trafficking.

Animals↗
PubMed1993

Re-evaluation of calcium currents in pre- and postsynaptic neurones of the chick ciliary ganglion.

1. Presynaptic nerve terminals of ciliary ganglia of the chick embryo were identified by the accumulation of dextran-tetramethylrhodamine applied to the cut end of the oculomotor nerve. Ca2+ currents were then recorded from the identified nerve terminals. 2. Whole-cell recordings were carried out simultaneously from a presynaptic terminal and its postsynaptic cell. The generation of presynaptic Ca2+ currents induced a postsynaptic response with a short delay. Electrical coupling was present in eight of fifteen pairs. The coupling ratio did not exceed 5%. 3. High-threshold Ba2+ currents were observed in presynaptic terminals without any evidence for the presence of low-threshold Ca2+ channels. The Ba2+ current was completely blocked by 50 microM Cd2+. 4. The presynaptic Ca2+ current induced by a long depolarizing pulse showed inactivation, but this inactivation was diminished when Ca2+ was replaced with Ba2+. 5. The presynaptic Ba2+ current was insensitive to dihydropyridines (DHPs). omega-Conotoxin GVIA (omega CgTX) suppressed a large fraction of the Ba2+ current irreversibly. About 10% of the Ba2+ current was resistant to both DHPs and omega CgTX. 6. The omega CgTX-sensitive component was not sensitive to changes in the holding potential between -120 and -50 mV. The omega CgTX-resistant component tended to be inactivated at depolarized holding potentials. 7. In some perisynaptic Schwann cells, small Ca2+ currents were observed. These Ca2+ currents increased monotonically with depolarization. 8. Only high-threshold Ca2+ channel currents were observed in postsynaptic ciliary cells. Exposure to 50 microM Cd2+ completely abolished the Ca2+ current. 9. About 25% of the Ba2+ currents were blocked by nifedipine (10 microM) in ciliary cells. The nifedipine-resistant component was partly blocked by omega CdTX (10 microM) leaving a small component (about 20%) which was resistant to both nifedipine and omega CgTX. 10. In ciliary cells, the fraction of Ba2+ currents blocked by omega CgTX was not affected by the presence or absence of nifedipine. Similarly, nifedipine blocked the Ba2+ currents to the same extent whether omega CgTX was present or not. The Ba2+ currents potentiated by Bay K 8644 were eliminated by nifedipine. 11. It is concluded that the presynaptic terminal of chick ciliary ganglion did not possess DHP-sensitive Ca2+ channels in contrast with the postsynaptic cell. Two subpopulations of presynaptic Ca2+ channels were distinguishable by their sensitivity to omega CgTX and membrane potential.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1990

Presynaptic nicotinic receptors and the modulation of transmitter release.

Nicotine is increasingly recognized to promote transmitter release in the brain by a direct action on presynaptic terminals. Pharmacological evidence indicates that this action is mediated by nicotinic receptors. From their sensitivity to mecamylamine, neosurugatoxin and neuronal bungarotoxin these presynaptic receptors can be distinguished from alpha-bungarotoxin-sensitive muscle-type nicotinic receptors, and can be correlated with [3H] nicotine binding sites in the brain. The release of many transmitters in different brain regions is susceptible to stimulation by nicotine, but this effect is not ubiquitous. However, lesioning and subcellular fractionation studies suggest that the majority of brain nicotine receptors are located presynaptically, so that a direct influence of nicotine on transmitter release assumes considerable importance. Although the sensitivity of presynaptic receptors is such that they are likely to be partially activated by doses of nicotine obtained by smoking, the desensitization-induced up-regulation of nicotinic binding sites that follows chronic nicotine treatment raises questions about their functional status during tobacco usage. Chronic administration of the agonist (+)anatoxin-a also up-regulated [3H] nicotine binding sites, and led to increased nicotine-evoked transmitter release in vitro. This could have implications for the involvement of these receptors during withdrawal.

Animals↗
PubMed1991

Glycine receptor immunoreactivity is localized at amacrine synapses in cat retina.

Immunocytochemical techniques were used to localize strychnine-sensitive glycine receptors in cat retina. Light microscopy showed staining in processes ramifying throughout the inner plexiform layer and in cell bodies of both amacrine and ganglion cells. At the electron-microscopic level, receptor immunoreactivity was seen to be clustered at sites postsynaptic to amacrine cells. In contrast, bipolar cells were neither presynaptic nor postsynaptic elements at sites of glycine receptor staining. Double-label studies verified the presence of glycine immunoreactivity in amacrine terminals presynaptic to glycine receptors. These findings support a role for glycine as an inhibitory neurotransmitter in amacrine cells.

Animals↗
PubMed1989

Synaptic plasticity at the crayfish opener neuromuscular preparation.

The crayfish opener neuromuscular preparation exhibits most of the plasticities yet described for any synapse, including facilitation, long-term potentiation, presynaptic inhibition, and modulation. Since the presynaptic terminals and postsynaptic muscle fibers can both be intracellularly penetrated, one can now more easily examine the cellular/molecular bases for these plasticities. Data from such studies suggest that facilitation may be influenced by something other than residual free calcium and that presynaptic inhibition is produced by a conductance increase to chloride in the terminals of the excitor axon. Several drugs (ethanol, pentobarbital) have significant effects on these synaptic plasticities over concentration ranges which produce obvious behavioral effects in crayfish and mammals. Hence, this preparation should be a useful model system to determine cellular/molecular bases for various synaptic plasticities and the effects of drugs on these plasticities.

Animals↗
PubMed2001

Glycine is taken up through GLYT1 and GLYT2 transporters into mouse spinal cord axon terminals and causes vesicular and carrier-mediated release of its proposed co-transmitter GABA.

Glycine and GABA are likely co-transmitters in the spinal cord. Their possible interactions in presynaptic terminals have, however, not been investigated. We studied the effects of glycine on GABA release using superfused mouse spinal cord synaptosomes. Glycine concentration dependently elicited [(3)H]GABA release which was insensitive to strychnine or 5,7-dichlorokynurenic acid, but was Na(+) dependent and sensitive to the glycine uptake blocker glycyldodecylamide. The glycine effect was external Ca(2+) independent, but was reduced when intraterminal Ca(2+) was chelated with 1,2-bis-(2-aminophenoxy)ethane-N,N,N',N'-tetracetic acid or depleted with thapsigargin, or when vesicular storage was impaired with bafilomycin. Glycine-induced [(3)H]GABA release was prevented, in part, by blocking GABA transport. The glycine effect was halved by sarcosine, a GLYT1 substrate/inhibitor, or by amoxapine, a GLYT2 blocker, and abolished by a mixture of the two. The sensitivity to sarcosine, used as a transporter inhibitor or substrate, persisted in synaptosomes prelabelled with [(3)H]GABA in the presence of beta-alanine, excluding major gliasome involvement. To conclude, in mice spinal cord, transporters for glycine (both GLYT1 and GLYT2) and for GABA coexist on the same axon terminals. Activation of the glycine transporters elicits GABA release, partly by internal Ca(2+)-dependent exocytosis and partly by transporter reversal.

Amino Acid Transport Systems, Neutral↗
PubMed2002

Reciprocal innervation of outer hair cells in a human infant.

Reciprocal synapses are characterized by the presence of both afferent and efferent types of synaptic specializations between two cells. They have been described at the neural poles of outer hair cells (OHCs) in humans with advanced age and two monkey species. Our objective was to study the innervation of the OHCs and determine if reciprocal synapses were present in a young (8-month-old infant) human subject. We studied the synaptic and cytoplasmic morphology of 162 nerve terminals innervating 29 OHCs using serial section transmission electron microscopy. Seventy-six percent of all OHCs were innervated by terminals with reciprocal synapses. This prevalence increased from the first toward the third row (p < 0.001), and 100% of OHCs in the third row demonstrated at least one reciprocal synapse. The prevalence of terminals with reciprocal synapses was higher in the human infant than in older human subjects and was very similar to what has been reported for the chimpanzee. Reciprocal synapses occur in sufficient numbers to be physiologically significant in primates. The nerve terminals were found to segregate into two groups on the basis of their cytoplasmic morphological characteristics: (1) vesicle-rich/neurofilament-poor (VR/NP) and (2) vesicle-poor/neurofilament-rich (VP/NR). All afferent and reciprocal terminals were of the VP/NR variety. The majority of the efferent terminals originated from VR/NP nerve fibers (classical olivocochlear morphology), but 23.5% of the efferent terminals were VP/NR. The hypothesis that peripheral processes of type II spiral ganglion cells form classical afferent, reciprocal, and a number of purely presynaptic terminals on OHCs is discussed. The presence of different types of synaptic specializations on OHCs formed by nerve fibers of the same type (VP/NR) suggests the existence of reciprocal neuronal circuits between OHCs sharing the dendritic arborization of a type II spiral ganglion cell.

Cytoplasm↗
PubMed1977

Genetic variation in brain L-glutamate decarboxylase activity from two inbred strains of mice.

Two inbred strains of mice, C57BL/6Bg and DBA/1Bg, were compared for genetic varaition in brain L-glutamate decarboxylase (GAD) activity. Although no large difference was found between the strains in whole brain GAD activity at adult age (27--45 days postnatally), regional examination revealed a difference in GAD activity in the cerebral cortex (15% higher in DBA); subcellular examination revealed a difference in synaptosomal fraction (21% higher in DBA). When GAD activity was measured in synaptosomal fractions prepared from dissected cerebral cortex, DBA was 34% higher than C57BL. In addition, differences in GAD activity between the two strains could be observed even in the whole brain (10--15% higher in DBA) during earlier development (15--23 days postnatally). These data indicate that at adult age, genetic difference in GAD activity between the two strains exists mainly in nerve terminals of the cerebral cortex. It is postulated that the difference may be due to a genetically mediated mechanism regulating GAD in the presynaptic terminals of GABA neurons of the cerebral cortex.

Age Factors↗
PubMed1986

Autoreceptor-mediated changes in dopaminergic terminal excitability: effects of potassium channel blockers.

The effects of the potassium channel blockers, 4-aminopyridine (4-AP) and tetraethylammonium (TEA), on autoreceptor-mediated changes in dopaminergic terminal excitability were examined in urethane-anesthetized rats. Local infusions of 4-AP or TEA into neostriatal terminal fields of nigral dopaminergic neurons led to marked decreases in terminal excitability, as measured by the increase in stimulating current required to activate the neurons antidromically from the site of the infusion. The decreased excitability resulting from 4-AP could be reversed by subsequent i.v. injection of haloperidol, and was blocked in rats that had been depleted of endogenous dopamine by prior treatment with alpha-methyl-p-tyrosine (AMpT). Thus, the decrease in excitability elicited by the potassium channel-blockers was indirect, and apparently due to increased autoreceptor stimulation resulting from enhanced transmitter release. In addition, co-infusion of 4-AP and apomorphine in AMpT-treated animals led to decreased terminal excitability that did not differ from the effects of apomorphine alone, indicating that 4-AP did not block the effects of exogenous autoreceptor agonist administration. These results provide in situ electrophysiological evidence that autoreceptor-mediated processes occurring at dopaminergic terminals are not mediated by 4-AP- or TEA-sensitive potassium channels. Furthermore, our findings suggest that, as in other types of presynaptic terminals, blockade of voltage-sensitive potassium channels in dopamine terminals leads to enhanced release of transmitter.

4-Aminopyridine↗
PubMed1992

Anatomical evidence of synaptic plasticity in the cochlear nuclei of white-deaf cats.

Synapses are dynamic structures reflecting environmental events. It was observed that densities associated with apposing synaptic membranes were altered in response to changing conditions of auditory stimulation (Gulley et al. 1978. J. Comp. Neurol. 180: 707-742). Synapses also exhibit plasticity during early development of the auditory system (Larsen and Pappas, 1985. Proceedings: 43rd Annual Meeting of the Electron Microscopy Society of America, pp. 493-494). Larsen and Pappas reported that, in young kittens, the end bulb of Held (EBH) terminal was distinguished by excessive density at apposing synaptic membranes which assume gradually the pattern observed in adult cats. The maturation of synapses parallels emerging function and may depend upon auditory stimulation (Larsen and Kirchhoff, 1987. Neurosci. Abstr. 13: 1260). Larsen and Kirchhoff found that EBH synapses on large spherical cells of white-deaf cats resembled the immature synapses found in young kittens (Fig. 1). They also found terminals that had an increased number and length of the membrane densities associated with synapses. Because the number of synaptic vesicles in these presynaptic terminals was equivalent to the number of vesicles found in normal-hearing cats, Larsen and Kirchhoff (1987) suggest that this is evidence of synaptic plasticity. We have completed a quantitative study of the synapses of EBH terminals found in adult cats that had been deaf for at least 3 years.

Albinism↗
PubMedDate not supplied

Fixation effects on synaptic vesicle density in neuromuscular junctions of young and old mice.

It was previously reported that in soleus neuromuscular junctions of old mice, synaptic vesicle density was decreased while transmitter release was increased (compared to results in young mice). In the present study, two hypotheses that might resolve this disparity were tested. The first was that the density of readily releasable vesicles close to the preterminal membrane, rather than those in the whole terminal, would correlate with the physiological results. This hypothesis was excluded because both vesicle density in the 200 nm region just within the presynaptic terminal membrane, and total vesicle density were similarly reduced in old soleus junctions. The second hypothesis was that more transmitter was released during fixation at old than at young neuromuscular junctions, leading to an age-related depletion of vesicles. This was tested by counting vesicles in muscles fixed after transmission block was attained in Krebs solution lacking calcium, and by direct recording of quantal release during conventional fixation. This second hypothesis was excluded: in neuromuscular junctions exposed to zero-calcium Krebs solution before fixation, the age-related reduction in vesicle density was still present, and intracellular recording revealed only a slight increase in quantal transmitter release during fixation. Therefore, as discussed, other mechanisms must be considered.

Aging↗
PubMed1990

Plasticity of identified neurons in slice cultures of hippocampus: a combined Golgi/electron microscopic and immunocytochemical study.

The combined Golgi/electron microscope (EM) technique and immunocytochemistry for glutamate decarboxylase (GAD) were used to study the differentiation of pyramidal neurons and GABAergic inhibitory non-pyramidal cells in slice cultures of rat and mouse hippocampus. Golgi-impregnated and gold-toned cultures showed the characteristic curved structure of the Ammon's horn. Hippocampal regions CA1, CA3 and fascia dentata could easily be recognized. Pyramidal neurons in CA1 displayed all characteristics of this cell type known from Golgi studies in situ. A triangular cell body gives rise to a main apical dendritic shaft which gives off several side branches. Basal dendrites and the axon originate at the basal pole of the cell body. Apical and basal dendrites are densely covered with spines. As a characteristic feature of the cultured pyramidal cells, numerous spines were observed on the cell body. Most likely due to flattening of the slice during incubation, the pyramidal neurons in CA1 are no longer arranged in a densely packed layer. This results in more space between cell bodies which is filled in by numerous horizontal and basal dendrites originating from the pyramidal cell perikaryon. CA1 pyramidal neurons in slice cultures of the rat or mouse thus resemble the pyramidal neurons in the CA1 region of the primate hippocampus where a similar loose distribution of cell bodies is found. In the electron microscope, cell bodies and dendritic shafts of the gold-toned pyramidal cells formed symmetric synaptic contacts with presynaptic terminals. Numerous boutons were observed that established asymmetric synaptic contacts on gold-toned spines of peripheral pyramidal cell dendrites. This suggests that considerable synaptic reorganization takes place because in situ spines on peripheral dendritic segments are contacted mainly by extrinsic afferents. Like in situ, at least some of the terminals that establish symmetric synaptic contacts are GABAergic. In our immunocytochemical study we observed numerous GAD-positive terminals that formed a dense pericellular plexus around immunonegative cell bodies of pyramidal neurons. In the electron microscope these structures were identified as presynaptic boutons which formed symmetric synaptic contacts on cell bodies and dendritic shafts. They most likely originated from the GAD-positive neurons scattered in all layers of the slice culture. Our results have shown that the main cell types in the hippocampus, pyramidal neurons and GABAergic inhibitory non-pyramidal cells, survive and differentiate under the present culture conditions.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1994

Platelet-activating factor as a potential retrograde messenger in CA1 hippocampal long-term potentiation.

Long-term potentiation (LTP) refers to a persisting enhancement of neurotransmission that follows high-frequency activation of certain synapses. Although both pre- and postsynaptic mechanisms contribute to LTP, it is believed that the enhanced release of neurotransmitter that accompanies this process results from the production of a diffusible messenger in postsynaptic neurons which traverses the synaptic cleft and alters the function of presynaptic terminals. One candidate for such a messenger is arachidonic acid, a metabolite produced by phospholipase A2 which augments synaptic transmission when coupled with presynaptic stimulation. However, the effects of arachidonic acid require activation of the postsynaptic receptor for N-methyl-D-aspartate. Previously we found that platelet-activating factor (1 O-alkyl-2-acetyl-sn-glycero-3-phosphocholine), another phospholipase A2-derived messenger, selectively enhances excitatory postsynaptic currents in hippocampal neurons by a presynaptic mechanism. We now present evidence that platelet-activating factor, acting at a receptor localized to synaptic regions, participates in LTP in the CA1 region of rat hippocampal slices and may serve as part of a retrograde signalling cascade.

Action Potentials↗
PubMed1980

Immunocytochemical localization of coated vesicle protein in rodent nervous system.

Immunocytochemistry has been used to study the distribution of the major 180,000-mol wt protein of coated vesicles in rodent cerebellum. An antibody to the coat protein was prepared in rabbits and characterized by immunodiffusion and immunofixation of polyacrylamide gels. At the light microscope level the protein was primarily localized in punctate profiles surrounding Purkinje cells and within the cerebellar glomeruli. At the electron microscope level the punctate distribution was confined to presynaptic terminals of basket and Golgi II neurons as well as mossy fiber terminals of the glomeruli. This label was heaviest on the lattice coat of coated vesicles but, in addition, label was found within the presynaptic axoplasm and along the cytoplasmic surface of the plasmalemma. Coated vesicles in cell somata were labeled as well as the cytosol around groupings of these vesicles. These data suggest that there may be two forms (or more) of coated vesicle protein in neurons, a lattice form associated with coated vesicles and a soluble form associated with the cytoplasmic matrix.

Animals↗
PubMed1994

Adenosine acting at an A1 receptor decreases N-type calcium current in mouse motoneurons.

The neuromodulator adenosine is known to decrease neurotransmitter release at the neuromuscular junction by activation of an A1 adenosine receptor coupled to a pertussis toxin-sensitive G protein. Among the mechanisms that could contribute to the depression of neurotransmitter release is reduced entry of calcium through channels located in the presynaptic terminal. In the present study, we have examined the effects of adenosine on high-voltage-activated (HVA) calcium currents in motoneurons, the presynaptic cells of the neuromuscular junction. The motoneurons were isolated from embryonic mice, placed in primary tissue culture for 16 hr, and analyzed by means of the whole-cell patch-clamp technique. Adenosine (40 microM) reduced both transient and sustained components of HVA calcium current. This effect was blocked by the A1 antagonist 8-cyclopentyltheophylline (CPT; 100 nM) and was mimicked by the A1 agonist N6-cyclohexyladenosine (CHA; 50 nM to 10 microM) but not by the A2a agonist 2-p-(2-carboxyethyl)phenethylamino-5'-N-ethylcarboxamido adenosine (CGS-21680; 1 micron). Pretreatment with pertussis toxin (200 ng/ml, > 16 hr) abolished the depression of HVA calcium current by adenosine receptor activation. Brief (3 min) exposure of the cells to 10 microM omega-conotoxin GVIA irreversibly blocked a part of the HVA current, which can therefore be attributed to N-type channels; the remaining current was unaffected by adenosine receptor activation. Hence, it appears that adenosine decreases only the N-current portion of HVA current and that this inhibition occurs via an A1 receptor linked to a pertussis toxin-sensitive G protein. Other investigators have shown that N-type channels do not play a primary role in eliciting transmitter release at the mammalian neuromuscular junction. Thus, it is uncertain what motoneuronal functions are influenced by adenosine modulation of N-type channels.

8-Bromo Cyclic Adenosine Monophosphate↗