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PubMed1993

Effect of destruction of dentate granule cells on kindling induced by stimulation of the perforant path.

Bilateral destruction of dentate granule cells in both the dorsal and ventral hippocampal formation had no effect on the threshold for hippocampal afterdischarge before or after kindling. Neither did it affect the number of stimulations required to attain kindling. However, the duration of afterdischarge was significantly longer in colchicine-lesioned animals compared to those receiving artificial cerebrospinal fluid. This was true for the threshold for afterdischarge as well as at the first and last kindling trials. These results suggest that dentate granule cells may inhibit the duration of afterdischarge induced by perforant path stimulation or that other postlesion changes occur which result in a prolongation of hippocampal afterdischarge.

Amygdala↗
PubMed1995

Cholinergic manipulations in the medial septal area: age-related effects on working memory and hippocampal electrophysiology.

Aged rats have impairments in several types of cognitive functions, including spatial working memory (WM), that are dependent upon the septohippocampal cholinergic system. The present series of experiments was designed to assess the effectiveness of pharmacological manipulations of the medial septal area (MSA) in order to influence the physiology of the septohippocampal pathway and, therefore, the brain functions in which this pathway participates. Aged (22MO) and young (4MO) Fischer-344 rats received microinfusions into the MSA with either saline, the muscarinic agonist, oxotremorine (OXO), or the muscarinic antagonist, scopolamine (SCOP). Working memory was tested in a T-maze spatial alternation task, prior to infusion, immediately after infusion, and 90 min after infusion. Hippocampal theta activity and the population excitatory postsynaptic potential (pEPSP) of the dentate gyrus to perforant path stimulation were recorded immediately following behavioral testing at each of the three time periods. In 22MO rats, intraseptal OXO (0.5 micrograms, 2 micrograms, 5 micrograms) produced a dose-dependent improvement in choice accuracy, a shift of the hippocampal theta peak to a lower frequency and a higher peak power, and an increase in the initial slope of pEPSP. OXO, 0.1 microgram, did not have an effect on behavior or hippocampal physiology and OXO, 10 micrograms, produced an impairment in performance. In 4MO rats, OXO did not affect choice accuracy, nor the pEPSP slope, but altered hippocampal theta peak frequency and power similarly as in 22MO. The lowest behaviorally effective dose, 0.5 microgram OXO, did not influence WM performance when infused into the lateral ventricles (intracerebroventricularly) of either 22MO or 4MO rats. SCOP (2 micrograms, 5 micrograms, 15 micrograms) decreased choice accuracy in a dose-dependent fashion in both 22MO and 4MO rats. However, in 22MO rats, the behavioral dose-response curve for scopolamine was shifted towards greater sensitivity. SCOP produced a shift of the hippocampal theta to a higher frequency and a lower peak power, and a decrease in the initial slope of pEPSP. In 4MO rats, SCOP altered hippocampal theta similarly to 22MO, but did not affect the pEPSP slope. These results indicate that (1) cholinergic receptors in the MSA are a useful target for drugs to improve WM in aging rats, (2) age-related changes in the activity of the septohippocampal pathway may increase its sensitivity to drugs which alter its activity, and (3) alterations in hippocampal physiology may contribute differently to changes in WM in young and in old rats.

Aging↗
PubMed1999

betagamma dimers derived from Go and Gi proteins contribute different components of adrenergic inhibition of Ca2+ channels in rat sympathetic neurones.

1. Using perforated-patch recordings, we have examined the part played by endogenous G-protein subunits in the alpha2-adrenoceptor-mediated inhibition of N-type Ca2+ currents in sympathetic neurones. 2. Two components of ICa inhibition by noradrenaline were recorded: a prominent, high affinity and voltage-dependent pertussis toxin (PTX)-sensitive pathway and a minor, low affinity and mostly voltage-insensitive PTX-resistant pathway. 3. PTX-sensitive inhibition was reduced by microinjection of antibodies against either GalphaoA,B or Galphai1,2. The voltage-dependent fraction of inhibition was reduced by anti-Galphao but not by anti-Galphai antibody. 4. Antisense depletion of GalphaoA led to a marked reduction of noradrenaline-induced inhibition and voltage dependence. By contrast, Galphai depletion attenuated noradrenergic modulation without affecting the voltage dependence. 5. Expression of the betagamma-binding agents beta-adrenergic receptor kinase 1 (C-terminus, betaARK1C-ter) or Galphai1 with a Cys3 to Ser mutation partially prevented noradrenergic inhibition while alpha-transducin abolished it. Residual inhibition was mostly voltage independent in cells expressing betaARK1C-ter but was strongly reversed by depolarization in Galphai1 Cys3Ser-expressing cells. 6. Expression of the PTX-resistant Galphai1 Cys351Ile mutant in cells treated with PTX restored alpha2-adrenoceptor inhibition. This restored inhibition was weakly reversed by depolarization. Both the degree and voltage dependence of inhibition were correlated with the level of expression of the Galphai1 Cys351Ile subunit. 7. Our findings identify betagamma dimers associated with GalphaoA and Galphai as mediators of the PTX-sensitive alpha2-adrenoceptor-mediated inhibition of N-type Ca2+ channels. Different betagamma combinations may account for the differential voltage-dependent effects of Go and Gi on ICa.

Animals↗
PubMed1985

The morphology of cerebrospinal fluid drainage pathways in human arachnoid granulations.

Arachnoid granulations and villi from 23 brains from subjects aged 9 to 84 years were examined post mortem by serial sections with the light microscope and as whole or fractured preparations in the scanning electron microscope. The object of the study was to investigate the pathways within the arachnoid granulations by which cerebrospinal fluid (CSF) drains from the subarachnoid space to the sinus endothelium. At the base of each granulation, a thin neck of arachnoid projects through an aperture in the dural lining of the sinus and expands to form a core of collagenous trabeculae and interwoven channels. An apical cap of arachnoid cells, about 150 microns thick, surmounts the collagenous core, and channels extend through the cap to reach subendothelial regions of the granulation. Channels within the granulation are lined by compacted collagen and may contain macrophages. Following recent subarachnoid hemorrhage, erythrocytes are found in the channels, suggesting that the channels are in continuity with the subarachnoid space and are CSF drainage pathways. The cap region of the granulation is only attached to the endothelium over an area 300 microns in diameter; the rest of the granulation core is separated from the endothelium by a subdural space and a fibrous dural cupola. Scanning electron microscopy reveals an intact endothelial surface to the granulations with small perforating venous channels present on the apex of some granulations. The differences between human arachnoid granulations and arachnoid villi in animals are discussed, together with preliminary observations regarding the transition of villi into granulations in man.

Adolescent↗
PubMed1997

Perivascular spaces in the basal ganglia of the human brain: their relationship to lacunes.

There is evidence for lymphatic drainage of interstitial fluid from the brain along perivascular spaces in a number of mammalian species. Ultrastructural studies suggest that there are similar drainage pathways in the human cerebral cortex. Perivascular spaces in the basal ganglia, however, differ from those in the cortex in that they dilate to form lacunes and rarely accumulate beta-amyloid (amyloid angiopathy) in Alzheimer's disease; in the cortex, lacunes are rare but amyloid angiopathy is common. The aim of the present study is to compare the structure of perivascular spaces in the basal ganglia and at the anterior perforated substance with perivascular spaces in the cerebral cortex. Eight postmortem brains from patients aged 23-80 years (mean 68 y) were examined by light microscopy, by scanning and transmission electron microscopy and by direct visualisation of etched paraffin blocks. The results show that arteries in the basal ganglia are surrounded by 2 distinct coats of leptomeninges separated by a perivascular space which is continuous with the perivascular space around arteries in the subarachnoid space. The inner layer of leptomeninges closely invests the adventitia of the vessel wall and the outer layer is continuous with the pia mater on the surface of the brain at the anterior perforated substance. Veins in the basal ganglia have no outer layer of leptomeninges and thus the perivascular space is continuous with the subpial space. The anatomy of the periarterial spaces in the basal ganglia differs significantly from that in the cerebral cortex where there is only a single periarterial layer of leptomeninges. Differences in structure of perivascular spaces around arteries may reflect relative efficiencies in the drainage of interstitial fluid from different sites in the brain. Furthermore, the structure of the perivascular spaces may contribute to the relatively high frequency of lacunes in the basal ganglia, and the low frequency of amyloid angiopathy at this site in Alzheimer's disease.

Adult↗
PubMed1979

Activity of dentate granule cells during learning: differentiation of perforant path input.

Experiments were conducted which extended previous findings regarding the activity of the perforant path and its synaptic relationship to the granule cells of the dentate gyrus during conditioning. A differential conditioning paradigm was utilized in which rats were trained to respond to one of two different tone frequencies. Results demonstrated that (1) tone elicited averaged evoked potentials recorded from the perforant path terminal zone in the outer molecular layer of the dentate gyrus were similar for both the positive and negative tones regardless of frequency or reversal of the reinforcement condition; (2) extracellular unit discharge patterns of dentate granule cells were differentially associated with the positive and negative tones as demonstrated by post stimulus histograms (PSHs); (3) this differential pattern of unit discharges could be reversed following establishment of criterion differential behavioral responding after reversal of the reinforcement contingency between the two tone stimuli and (4) the differential unit discharge pattern was not present when behavioral responding was not differentiated to the two tone stimuli, e.g., immediately following reversal of the reinforcement contingency. The results are discussed within the context of other anatomically defined functional circuits within the hippocampus which could serve as the basis for alteration of the non differentiated excitatory perforant path input into a differential dentate granule cell discharge pattern for behaviorally relevant sensory stimuli.

Acoustic Stimulation↗
PubMed1991

Partial kindling of the ventral hippocampus: identification of changes in limbic physiology which accompany changes in feline aggression and defense.

This study examined the interictal consequences of partial kindling of the ventral perforant path on attack and defensive behavior in the domestic cat. Partial kindling produced a lasting increase in defense response of cats to both rats and conspecific threat howls. In addition, there was a lasting suppression of approach-attack behaviors directed toward rats. The suppression of some components of approach-attack were shown to be independent of the increases in defensive response. The effects of partial kindling of the ventral perforant path on spread of seizure activity into the amygdala, and on the output of the amygdala to both the ventromedial hypothalamus (VMH) and bed nucleus of the stria terminalis (BNST) were also examined. In addition, the effects of repeated hippocampal seizures on recurrent inhibition in the trisynaptic circuit (areas CA1 and CA3) were investigated. Growth of seizure activity in the amygdala and VMH as partial kindling progressed was essential for behavioral change. In addition, interictal long-term potentiation of potentials evoked in the VMH and in the BNST by pulsed stimulation of the amygdala followed partial kindling or afterdischarge threshold determination in the ventral perforant path. A lasting interictal increase in inhibition in area CA3 and a lasting interictal failure of inhibition in area CA1 of the ventral hippocampus also followed partial kindling. These changes in limbic physiology were related to the behavioral changes produced by partial kindling. The analysis revealed the importance of the amygdalo-VMH pathway in increased defensive response to rats. The amygdalo-BNST pathway is not important in mediating defensive response to prey, but it is implicated in suppression of some types of predatory aggression. Finally, changes in neural inhibition in the ventral hippocampus in areas CA1 and CA3 are associated with changes in both defensiveness and predatory aggression.

Aggression↗
PubMed1994

Multiple effects of SK&F 96365 on ionic currents and intracellular calcium in human endothelial cells.

1. Multiple effects of the imidazole compound SK&F 96365 have been evaluated on endothelial cells from human umbilical vein using a combined patch clamp and Ca(2+)-microfluorimetric technique (Fura-2). 2. At concentrations of 100 mumol/l or higher of SK&F 96365, the block of the receptor-mediated Ca2+ entry overlaps with the activation of another Ca(2+)-entry mechanism, which is associated with a non selective cationic current. 3. This rise in [Ca2+]i depends on the extracellular Ca(2+)-concentration, and the entry pathway is in contrast with the receptor-mediated Ca(2+)-entry pathway permeable to Ni2+, as shown by quenching of the Fura-2 fluorescence signal. 4. The concentration of SK&F 96365 for half maximal increase in [Ca2+]i was 141 +/- 19 mumol/l (n = 16). 5. SK&F 96365 activated a current that reversed at +11.8 +/- 2.1 mV (n = 21) when measured using nystatin-perforated patches with either Cs+ or K+ in the pipette and 140 Na+, 1.5 Ca2+ in the bath (chloride equilibrium potential ECl = -36 mV). 6. SK&F 96365 (200 mumol/l) blocked an inwardly rectifying K+ current in endothelial cells independently of [Ca2+]i. This block caused depolarization of the endothelial cells from -55.3 +/- 2.57 mV (n = 33) to -10 +/- 5.5 mV (n = 6). This block was concentration-dependent, half maximal block occurred at a concentration of about 40 mumol/l SK&F 96365. 7. In cells which showed an outwardly rectifying current, this outward component was also completely blocked by 200 mumol/l SK&F 96365. 8. It is concluded that SK&F 96365 reversibly activates a non-selective cation channel at concentrations higher than 100 mumol/l, but also blocks K+ currents in endothelial cells independently of [Ca2+]i. These multiple effects overlap with the proposed block of receptor-mediated Ca2+ entry. The block of K(+)-channels may in unclamped cells reduce the driving force for Ca2+, and thereby interfere with the Ca(2+)-influx.

Calcium↗
PubMed2005

Kupffer cell ablation attenuates cyclooxygenase-2 expression after trauma and sepsis.

BACKGROUND: Prostaglandins, synthesized by cyclooxygenase (COX), play an important role in the pathophysiology of inflammation. Severe injuries result in immunosuppression, mediated, in part, by maladaptive changes in macrophages. Herein, we assessed Kupffer cell-mediated cyclooxygenase-2 (COX-2) expression on liver function and damage after trauma and sepsis. MATERIALS AND METHODS: To ablate Kupffer cells, Sprague Dawley rats were treated with gadolinium chloride (GdCl3) 48 and 24 h before experimentation. Animals then underwent femur fracture (FFx) followed 48 h later by cecal ligation and puncture (CLP). Controls received sham operations. After 24 h, liver samples were obtained, and mRNA and protein expression were determined by PCR, Western blot, and immunohistochemistry. Indocyanine-Green (ICG) clearance and plasma alanine aminotransferase (ALT) levels were determined to assess liver function and damage, respectively. One-way analysis of variance (ANOVA) with Student-Newman-Keuls test was used to assess statistical significance. RESULTS: After CLP alone, FFx+CLP, and GdCl3+FFx+CLP, clearance of ICG decreased. Plasma ALT levels increased in parallel with severity of injury. Kupffer cell depletion attenuated the increased ALT levels after FFx+CLP. Femur fracture alone did not alter COX-2 protein compared with sham. By contrast, COX-2 protein increased after CLP and was potentiated by sequential stress. Again, Kupffer cell depletion abrogated the increase in COX-2 after sequential stress. Immunohistochemical data confirmed COX-2 positive cells to be Kupffer cells. CONCLUSIONS: In this study, sequential stress increased hepatic COX-2 protein. Depletion of Kupffer cells reduced COX-2 and attenuated hepatocellular injuries. Our data suggest that Kupffer cell-dependent pathways may contribute to the inflammatory response leading to increased mortality after sequential stress.

Animals↗
PubMed1989

The temporal-hippocampal region and retention: the role of temporo-entorhinal connections in rats.

Results from previous studies suggest that the entorhinal cortex may be involved in mnemonic processes. The present study was carried out to investigate whether disruption of fibre connections between the temporal cortex and lateral entorhinal area may impair retention of a pre-operatively acquired simultaneous brightness discrimination task. The lesion resulted in a severe impairment in retaining the discrimination task (Experiment 1). The retention deficit could not be traced into the hippocampal formation by making perforant path lesions or hippocampal lesions (Experiment 2). The results indicate that the lateral entorhinal cortex is more crucial for reference memory than the hippocampal formation.

Animals↗
PubMed1987

Microsurgical treatment of lens capsule perforations--Part II: Clinical applications and results.

A microsurgical technique using human fibrinogen concentrate for the closure of anterior lens capsule wounds and through-and-through perforations was developed, experimentally tested and clinically applied. I consider here the first consecutive 31 patients treated. All these patients had perforating injuries of the lens and still localized lens damage; they showed no spontaneous healing tendencies. Successful treatment of lens capsule wounds, where an otherwise clear lens is locally scarred, has been rare. The technique described here was effective in more than 50% of the patients with anterior lens capsule lesions. Removal of degenerated lens cortex matter before fibrinogen application further improved the healing rate. The healing rate was low, however, in through-and-through perforations of the lens when the posterior lesion was not treated at all (of 11 cases, 1 success, 10 traumatic cataracts). It was not much better when the posterior lesion was approached via a basal iridectomy and around the lens equator (of 4 cases, 1 success). But translental fibrinogen application, following the foreign body pathway, together with removal of degenerated cortex matter from the anterior and posterior capsule lesion area, resulted in the prevention of traumatic cataract in all 4 patients treated so far. There were no undesirable local or systemic side-reactions. (Intraocular complications could be avoided by not exceeding the recommended amount of fibrinogen concentrate, 0.01-0.02 ml). The case histories of 3 patients are shown in three photographs.

Aprotinin↗
PubMed1984

Sympathetic uveitis 66 years after injury.

We report a case of sympathetic uveitis occurring 66 years after perforating trauma to the other eye. To our knowledge this is the longest interval ever cited in the literature.

Aged↗
PubMed1980

Autoradiographic evidence for a projection from the pretectal nucleus of the optic tract to the dorsal lateral geniculate complex in the cat.

A pathway from the pretectal region to the dorsal division of the lateral geniculate body has been studied by autoradiography in adult cats following injection of tritium-labeled amino acids into the meso-diencephalic border zone. The findings suggest that the pretecto-geniculate connection arises in the ipsilateral nucleus of the optic tract (NOT) and terminates in the principle dorsal layers of the geniculate body (A and A1), in lamina C and most massively in the medial interlaminar nucleus. In the A layers and lamina C, the pretectal fibers from a relatively even matting with partial interruptions occurring at the interlaminar leaflets. The ventral C layers do not appear to receive a substantial pretectal input as they were only weakly labeled, and partly in a perforant fiber pattern, after injections confined to the pretectum. Topographic ordering of the projection was evident at least along the medial to lateral axis of the NOT, fibers from the medial part terminating caudally, and those from the lateral part rostrally, within the lateral geniculate complex. The laminar pattern of termination correlates closely with the distribution of retinal Y-cell input and acetylcholinesterase activity in the geniculate body but contrasts sharply with the pattern of termination of tecto-geniculate fibers. Of potential importance in considering the functional significance of the pretecto-geniculate pathway is the fact that the NOT has been implicated in the mechanism of optokinetic nystagmus and the fact that the pathway terminates within the layers of the lateral geniculate body known to provide the main geniculo-cortical input to layer IV of the striate cortex.

Acetylcholinesterase↗
PubMed1991

Current treatment for Wolff-Parkinson-White syndrome: results and surgical implications.

From July 1986 to January 1991, 123 patients with Wolff-Parkinson-White syndrome underwent operation for ablation of aberrant conduction pathways. There were 85 male and 38 female patients ranging in age from 11 months to 68 years. Associated anomalies included Ebstein's anomaly, sudden death syndrome, coronary artery disease, cardiomyopathy, abdominal aortic aneurysm, neurofibromatosis, other arrhythmias, or other complex congenital heart disease. Forty-one patients had multiple accessory pathways. Operative results showed a 7% initial failure rate, which dropped to 3% after reoperation. One patient had undergone previous operation for Wolff-Parkinson-White syndrome at another institution. Procedures performed concomitantly included mitral or tricuspid valve repair or replacement (6), right ventricular conduit replacement, subaortic resection, Fontan repair, corrected transposition repair, coronary artery bypass, and placement of an automatic internal cardioverter defibrillator. There was no operative mortality. Late follow-up is 27 +/- 16 months, and complications included mitral regurgitation and myocardial infarction. By comparison, in the last 12 months 124 patients with the Wolff-Parkinson-White syndrome underwent catheter ablation using radiofrequency current. There were 9 patients with multiple pathways. One hundred twelve patients (90%) had all accessory atrioventricular connections ablated and have remained free of symptomatic tachycardia. There have been 12 failures (10%), of which 5 have had operation and 7 are being treated medically. Mean follow-up is 7 +/- 5 months, and complications included circumflex coronary artery occlusion, excessive bleeding, valve perforation, and cerebral vascular accident.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed2002

Characterization of a charybdotoxin-sensitive intermediate conductance Ca2+-activated K+ channel in porcine coronary endothelium: relevance to EDHF.

1. This study characterizes the K(+) channel(s) underlying charybdotoxin-sensitive hyperpolarization of porcine coronary artery endothelium. 2. Two forms of current-voltage (I/V) relationship were evident in whole-cell patch-clamp recordings of freshly-isolated endothelial cells. In both cell types, iberiotoxin (100 nM) inhibited a current active only at potentials over +50 mV. In the presence of iberiotoxin, charybdotoxin (100 nM) produced a large inhibition in 38% of cells and altered the form of the I/V relationship. In the remaining cells, charybdotoxin also inhibited a current but did not alter the form. 3. Single-channel, outside-out patch recordings revealed a 17.1+/-0.4 pS conductance. Pipette solutions containing 100, 250 and 500 nM free Ca(2+) demonstrated that the open probability was increased by Ca(2+). This channel was blocked by charybdotoxin but not by iberiotoxin or apamin. 4. Hyperpolarizations of intact endothelium elicited by substance P (100 nM; 26.1+/-0.7 mV) were reduced by apamin (100 nM; 17.0+/-1.8 mV) whereas those to 1-ethyl-2-benzimidazolinone (1-EBIO, 600 microM, 21.0+/-0.3 mV) were unaffected (21.7+/-0.8 mV). Substance P, bradykinin (100 nM) and 1-EBIO evoked charybdotoxin-sensitive, iberiotoxin-insensitive whole-cell perforated-patch currents. 5 A porcine homologue of the intermediate-conductance Ca(2+)-activated K(+) channel (IK1) was identified in endothelial cells. 6. In conclusion, porcine coronary artery endothelial cells express an intermediate-conductance Ca(2+)-activated K(+) channel and the IK1 gene product. This channel is opened by activation of the EDHF pathway and likely mediates the charybdotoxin-sensitive component of the EDHF response.

Amino Acid Sequence↗
PubMed1990

Three-dimensional structure of rhesus rotavirus by cryoelectron microscopy and image reconstruction.

The structure of rhesus rotavirus was examined by cryoelectron microscopy and image analysis. Three-dimensional reconstructions of infectious virions were computed at 26- and 37-A resolution from electron micrographs recorded at two different levels of defocus. The major features revealed by the reconstructions are (a) both outer and inner capsids are constructed with T = 13l icosahedral lattice symmetry; (b) 60 spikelike projections, attributed to VP4, extend at least 100 A from the outer capsid surface; (c) the outer capsid, attributed primarily to VP7, has a smoothly rippled surface at a mean radius of 377 A and is perforated by 132 aqueous holes ranging from 40-65 A in diameter; (d) the inner capsid has a "bristled" outer surface composed of 260 trimeric-shaped columns of density, attributed to VP6, which merge with a smooth, spherical shell of density at a lower, mean radius of 299 A, and which is perforated by holes in register with those in the outer capsid; (e) a "core" region contains a third, nonspherical shell of density at a mean radius of 225 A that encapsidates the double-stranded RNA genome; and (f) the space between the outer and inner capsids forms an open aqueous network that may provide pathways for the diffusion of ions and small regulatory molecules as well as the extrusion of RNA. The assignment of different viral structural proteins to specific features of the reconstruction has been tentatively made on the basis of excluded volume estimates and previous biochemical characterizations of rotavirus.

Animals↗
PubMed2006

Sustained activation of proton channels and NADPH oxidase in human eosinophils and murine granulocytes requires PKC but not cPLA2 alpha activity.

The prevailing hypothesis that a signalling pathway involving cPLA(2)alpha is required to enhance the gating of the voltage-gated proton channel associated with NADPH oxidase was tested in human eosinophils and murine granulocytes. This hypothesis invokes arachidonic acid (AA) liberated by cPLA(2)alpha as a final activator of proton channels. In human eosinophils studied in the perforated-patch configuration, phorbol myristate acetate (PMA) stimulation elicited NADPH oxidase-generated electron current (I(e)) and enhanced proton channel gating identically in the presence or absence of three specific cPLA(2)alpha inhibitors, Wyeth-1, pyrrolidine-2 and AACOCF(3) (arachidonyl trifluoromethyl ketone). In contrast, PKC inhibitors GFX (GF109203X) or staurosporine prevented the activation of either proton channels or NADPH oxidase. PKC inhibition during the respiratory burst reversed the activation of both molecules, suggesting that ongoing phosphorylation is required. This effect of GFX was inhibited by okadaic acid, implicating phosphatases in proton channel deactivation. Proton channel activation by AA was partially reversed by GFX or staurosporine, indicating that AA effects are due in part to activation of PKC. In granulocytes from mice with the cPLA(2)alpha gene disrupted (knockout mice), PMA or fMetLeuPhe activated NADPH oxidase and proton channels in a manner indistinguishable from the responses of control cells. Thus, cPLA(2)alpha is not essential to activate the proton conductance or for a normal respiratory burst. Instead, phosphorylation of the proton channel or an activating molecule converts the channel to its activated gating mode. The existing paradigm for regulation of the concerted activity of proton channels and NADPH oxidase must be revised.

Animals↗
PubMed1987

Enkephalin enhances responsiveness to perforant path input while decreasing spontaneous activity in the dentate gyrus.

The opioid peptide [D-Ala2-Met5]-enkephalin-amide (DAMEA) was electrophoretically applied to the dentate gyrus in vivo to investigate opioid effects on evoked responsiveness to perforant path input and on spontaneous granule cell activity. DAMEA increased the amplitude of population spikes evoked by stimulation of the perforant path, and decreased sequential (recurrent or feed-forward) inhibition as determined by a paired-pulse paradigm. However, DAMEA concurrently inhibited spontaneous activity of individual granule cells. The effects of DAMEA on population and unit responses were antagonized by intravenous naloxone. These results confirm previous findings of opioid enhanced responsiveness to perforant path input and decreased sequential inhibition, but demonstrate a paradoxical inhibition of spontaneous unit activity by opioids in the granule cell layer.

Action Potentials↗