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PubMed1993

Reappraisal of radiofrequency ablation of multiple accessory pathways.

Complete electrophysiologic study and radiofrequency ablation were performed in 145 consecutive patients with Wolff-Parkinson-White syndrome. Presence of multiple accessory atrioventricular pathways was documented in 20 patients (13.8%); 17 had two, two had three, and one had four accessory pathways. Location of accessory pathways was posteroseptal in 18, left free wall in 15, right free wall in nine, and right midseptal in two. Of the 44 pathways, 36 were found during baseline electrophysiologic study and eight were found after successful ablation of the initially attempted pathways. After delivery 20 +/- 23 pulses (per patient) of radiofrequency energy (37 +/- 6 W, 70 +/- 30 seconds), 43 accessory pathways were ablated successfully without complications. Duration of the procedure (4.5 +/- 1.7 vs 3.7 +/- 1.6 hours, p < 0.05) and radiation exposure time (53 +/- 30 vs 38 +/- 18 minutes, p < 0.05) were longer in patients with multiple pathways, whereas the success rate (95% vs 95%, p > 0.05) and incidence of recurrent conduction (11% vs 11%, p > 0.05) were similar in patients with single or multiple accessory pathways. These findings confirmed that multiple accessory pathways were common in patients with Wolff-Parkinson-White syndrome, and these pathways could be ablated successfully by radiofrequency energy with a success rate comparable to that of a single accessory pathway.

Adult↗
PubMed1978

Effect of catheter position on the initiation of atrial echoes with atrial pacing and premature stimulation in patients with accessory pathways.

Eleven patients with an accessory pathway and reciprocating tachycardia were studied using both fixed rate atrial pacing and the atrial extrastimulus technique. Six of the patients had an accessory pathway that conducted in both the anterograde and retrograde direction; but the effective refractory period of their accessory pathway in the anterograde direction was relatively long and was greater than the longest coupling intervals that initiated atrial echoes. Five patients had an accessory pathway that conducted only in the retrograde direction. The extrastimulus technique could be used with stimulation sites near to and remote from the accessory pathway in 10 of the 11 patients. Atrial echoes were initiated by a single atrial extrastimulus at both sites in 7 of the 10 patients, and in each patient the upper limit of the echo zone was longer with stimulation at the site near the accessory pathway. In the other three patients atrial echoes were initiated only during stimulation at the site near the accessory pathway because either atrial refractoriness or atrioventricular nodal refractoriness was encountered before the echo zone was entered during stimulation at the site remote from the accessory pathway. Differences in the longest cycle length that initiated an atrial echo during fixed rate atrial pacing were similarly demonstrated in three patients. In these three patients, pacing at the site near the accessory pathway initiated echoes at a longer cycle length than pacing at the site remote from the accessory pathway. In three other patients the electrophysiologic characteristics of atrioventricular conduction prevented a demonstration of these differences. Catheter position is an important variable in the initiation of atrial echoes in patients with accessory pathways.

Arrhythmias, Cardiac↗
PubMed1991

Characteristics of accessory pathways exhibiting decremental conduction.

The prevalence, electrophysiologic characteristics and functional significance of decremental conduction over an accessory pathway were examined in this retrospective study of 653 patients who had an accessory pathway demonstrated at electrophysiologic study. Decremental conduction was identified in 50 patients (7.6%). In 15 patients with anterograde decremental conduction, the accessory pathway was right parietal or septal in 14 patients and left parietal in 1 patient. In the 40 patients with retrograde decrement, the accessory pathway was left parietal in 19, posteroseptal in 13, right parietal in 2 and right anteroseptal in 6 patients. Anterograde conduction over the accessory pathway was absent in 11 of the 40 patients with retrograde decrement. Retrograde conduction over the accessory pathway was absent in 9 patients with anterograde decrement. There was no significant difference in the accessory pathway effective refractory period, or shortest cycle length with 1:1 conduction over the accessory pathway in anterograde and retrograde directions. The shortest RR interval in atrial fibrillation between 2 preexcited QRS complexes was longer in patients with anterograde decremental conduction than in a control group of patients with anterograde-conducting accessory pathways without decremental properties. These data demonstrate that decremental conduction over accessory pathways is uncommon. Anterograde decremental conduction usually occurs in right-sided or septal pathways that often do not conduct in the retrograde direction.

Adolescent↗
PubMed1990

Mechanism of ventricular extrasystoles with fixed coupling. A theoretical model derived from the concept of longitudinal dissociation in the reentrant pathway of extrasystoles.

An electrocardiogram taken from a 29-year-old man with old myocardial infarction is presented as an exemplary case of ventricular extrasystoles with fixed coupling. To explain the mechanism of ventricular extrasystoles with fixed coupling, a theoretical model is derived from the concept of longitudinal dissociation in the reentrant pathway. In the model, functional longitudinal dissociation divides the reentrant pathway into dual pathways F and S. When a sinus impulse is blocked in pathway F and passes only through pathway S, it becomes a manifest reentrant extrasystole because of marked conduction delay in pathway S. When the sinus rate does not exceed a certain value, such an impulse always becomes a manifest extrasystole with fixed coupling. Part of the impulse passing through pathway S enters pathway. F retrogradely. In some cases, thereafter, it reenters pathway S and initiates ventricular reentrant tachycardia. When, on the other hand, a sinus impulse passes through both of pathways F and S, it becomes a concealed reentrant extrasystole because of insufficient conduction delay in the pathways.

Adult↗
PubMed1992

Rate-dependent accessory pathway conduction due to phase 3 and phase 4 block. Antegrade and retrograde conduction properties.

Six patients who had antegrade phase 3 and phase 4 block in the accessory pathway were examined. In each patient, antegrade conduction over the accessory pathway was absent both at the sinus rate and at slower heart rates. During premature atrial stimulation a "window" of accessory pathway conduction was identified in all patients. The outer limits of the window ranged from 480 ms to 670 ms. The inner limits ranged from 410 ms to 620 ms. The durations of the window ranged from 20 ms to 160 ms. Three patients with orthodromic atrioventricular reentrant tachycardia showed preserved retrograde accessory pathway conduction. The remaining three patients had impaired retrograde accessory pathway conduction. One of the patients showed retrograde phase 4 block in the accessory pathway. In two patients, retrograde concealed conduction in the accessory pathway induced by ventricular stimulation prolonged the outer limit of the window in the antegrade accessory pathway conduction. These findings suggest that the mechanism of antegrade phase 3 and phase 4 block in the accessory pathway may be spontaneous diastolic depolarization in the accessory pathway and conduction disturbance at the ventricular and/or atrial insertion of the accessory pathway.

Adult↗
PubMed1990

An integrated modeling-experimental strategy for the analysis of metabolic pathways.

An inherent problem in studying the behavior of a metabolic pathway is the impossibility of developing a complete, detailed model that includes all the cellular processes that have an impact on the set of fluxes in such a pathway. Lacking this, one requires some means of modeling the interactions between a metabolic pathway and other cellular processes for the purpose of analyzing pathway characteristics within the cell (e.g., determining sensitivity coefficients for various steps in the pathway) with a minimal amount of time and effort. A general framework is developed for studying these issues in a rigorous manner. Using this framework, detailed knowledge about a metabolic pathway (i.e., a set of rate expressions for steps in the pathway) can be combined with the results from a relatively simple set of experiments in order to obtain estimates for the sensitivity of the pathway to enzyme activities, inhibition constants, and other parameters that determine the pathway's behavior, while accounting for the pathway's interaction with the rest of the cellular metabolism. A model system representing amino acid production is used to illustrate the problem and to provide results based on computational experiments. The modeling strategy described here should be useful in genetic design to improve pathway fluxes and metabolic network selectivity.

Amino Acids↗
PubMed1988

Transvenous catheter ablation of extranodal accessory pathways.

Twelve patients with an accessory pathway and recurrent symptomatic reciprocating tachycardia or atrial fibrillation, or both, underwent attempted transvenous catheter ablation of the accessory pathway. In one patient with a small right coronary artery, the pathway was along the right free wall. In 11 patients, the pathway was located at or within 15 mm of the coronary sinus os. For these patients, a quadripolar electrode catheter was placed in the coronary sinus and positioned, if possible, so that the proximal pair of electrodes straddled the pathway. For those patients with a pathway greater than 5 mm within the coronary sinus, the most proximal electrode was placed at the os. This proximal pair of electrodes was connected to the cathodal output of a defibrillator with an anterior chest wall patch serving as the current sink. Two shocks were then delivered for a cumulative energy of 500 to 600 J (stored energy). Among the eight patients with a pathway at or within 5 mm of the coronary sinus os, conduction over the pathway was abolished in five and modified in one. Among the four patients with a pathway farther from the os (10 to 15 mm) and along the right free wall, pathway conduction was modified only in two. Rupture of the coronary sinus did not occur in any patient. There were no serious complications. Minor damage surrounding the area of ablation was seen at the time of surgical division of the accessory pathway in two of five patients with unsuccessful ablation who subsequently underwent surgery.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Predictive accuracy of electrophysiologic localization of accessory pathways.

Operative ablation of accessory pathways depends critically on preoperative localization when technical limitations preclude complete intraoperative mapping. To assess the accuracy of localization, 345 patients undergoing operative ablation were studied; 316 (91.6%) had a single accessory pathway and 29 (8.4%) had multiple accessory pathways. The electrophysiologic study was diagnostically complete and accurate in 294 patients (93%) with a single accessory pathway and 19 (61%) with multiple accessory pathways. A left lateral accessory pathway was most accurately localized with excellent sensitivity (99%) and positive predictive value (98.5%). Diagnostic errors occurred in 33 patients because of 1) incorrect localization (n = 16), 2) failure to detect a second pathway (n = 9), and 3) diagnosis of a second pathway not verified intraoperatively (n = 8). Multiple pathways were more prevalent in the group with errors (33.3% vs. 5.8%, p = 0.0001), as were unidirectional pathways (48.5% vs. 24.3%, p = 0.003). It is concluded that preoperative localization of accessory pathways is sufficiently accurate to allow intraoperative mapping to be brief and focused.

Adult↗
PubMed1994

Atypical forms of supraventricular tachycardia due to atrioventricular node reentry in children after radiofrequency modification of slow pathway conduction.

OBJECTIVES: This study was performed to investigate the prevalence, mechanisms and clinical significance of supraventricular tachycardias inducible in children or adolescents after radiofrequency modification of slow pathway conduction for the treatment of atrioventricular (AV) node reentrant tachycardia. BACKGROUND: Limited data have been reported with regard to the physiology of AV node reentrant tachycardia in young patients. Radiofrequency catheter ablation allows evaluation of the effects of selective modification of the different pathways involved in AV node reentrant tachycardia. METHODS: Selective modification of slow pathway conduction was performed in 18 young patients (12.9 +/- 3.4 years old) with typical (anterograde slow-retrograde fast) AV node reentrant tachycardia. Radiofrequency energy was applied across the posteromedial or midseptal tricuspid annulus, guided by slow pathway potentials and anatomic position. Programmed stimulation was performed after modification of slow pathway conduction defined as noninducibility of typical AV node reentrant tachycardia. RESULTS: Modification of slow pathway conduction was achieved in each patient, with a median of four applications of radiofrequency energy. However, atypical forms of supraventricular tachycardia were inducible in 9 of 18 young patients after slow pathway modification: AV node reentrant tachycardia with 2 to 1 AV block (seven patients); anterograde fast-retrograde slow AV node reentrant tachycardia (five patients); and sustained accelerated junctional tachycardia (two patients). In comparison, atypical forms of tachycardia were inducible in only 2 of 59 adult patients with AV node reentrant tachycardia undergoing slow pathway modification in the same laboratory (p = 0.01). Additional applications of radiofrequency energy to the posteromedial tricuspid annulus rendered AV node reentrant tachycardia with 2 to 1 block and the fast-slow form of AV node reentrant tachycardia noninducible. Junctional tachycardia terminated spontaneously in both patients. During 9.8 +/- 3 months of follow-up, slow-fast AV node reentrant tachycardia has recurred in one patient, whereas fast-slow AV node reentrant tachycardia has occurred in two patients, both with inducible fast-slow tachycardia after the initial modification of slow pathway conduction. CONCLUSIONS: Initial applications of radiofrequency energy may selectively modify the anterograde conduction of slow pathway fibers in young patients with AV node reentrant tachycardia. This may result in AV node reentrant tachycardia with 2 to 1 AV block or a reversal of the reentrant circuit (fast-slow tachycardia). Induction of these tachyarrhythmias indicates that further applications of radiofrequency energy are required for the successful modification of slow pathway conduction in young patients. The increased prevalence of inducible atypical arrhythmias among young patients suggests differences in the anatomic or electrophysiologic substrate of AV node reentrant tachycardia that may evolve as a function of age.

Adolescent↗
PubMed2005

Activation of the lectin pathway in murine lupus nephritis.

In systemic lupus erythematosus (SLE), hypocomplementaemia and complement deposition have been described both in man and in experimental models. A major involvement of the classical pathway of complement activation has been demonstrated in this disease, however relatively little is known about the involvement of the lectin pathway. Therefore in the present study we have analyzed the activity of all three pathways of complement activation in murine models of SLE. In the mouse, MBL is expressed in two forms, namely MBL-A and MBL-C. In the present study young and old MRL-lpr and control MRL+/+ mice were compared for the levels of complement activity with specific attention for the lectin pathway. It was found that upon aging of both MRL-lpr and MRL+/+ mice, a marked decrease in the activity of the classical pathway (CP) occurs. Levels of alternative pathway (AP) and lectin pathway (LP) activity remain unchanged. Key-molecules of these pathways, C1q, C3, MBL-A and MBL-C were analyzed and were all found to be decreased in aged mice of both strains. The levels of MBL-A and MBL-C showed a high degree of correlation and decreased equally. In aged MRL-lpr mice in which autoimmunity is most pronounced, we observed high autoantibody titers and strong deposition of glomerular immune complexes in association with deposition of C1q, C3, MBL-A and MBL-C. In conclusion, these data suggest that in addition to the classical pathway and the alternative pathway also the lectin pathway of complement activation is involved in murine lupus nephritis.

Animals↗
PubMed2000

Tyr(30) of amicyanin is not critical for electron transfer to cytochrome c-551i: implications for predicting electron transfer pathways.

A Pathways analysis of the methylamine dehydrogenase-amicyanin-cytochrome c-551i protein electron transfer (ET) complex predicts two sets of ET pathways of comparable efficiency from the type I copper of amicyanin to the heme of cytochrome c-551i. In one pathway, the electron exits copper via the Cys(92) copper ligand, and in the other, it exits via the Met(98) copper ligand. If the Pathways algorithm is modified to include contributions from the anisotropy of metal-ligand coupling, independent of differences in copper-ligand bond length, then the pathways via Cys(92) are predicted to be at least 100-fold more strongly coupled than the pathways via any of the other copper ligands. All of the favored pathways via Cys(92) include a through-space jump from Cys(92) to the side chain of Tyr(30). To determine whether or not the pathways via Cys(92) are preferentially used for ET, Tyr(30) was changed to other amino acid residues by site-directed mutagenesis. Some mutant proteins were very unstable suggesting a role for Tyr(30) in stabilizing the protein structure. Y30F and Y30I mutant amicyanins could be isolated and analyzed. For the Y30I mutant, the modified Pathways analysis which favors ET via Cys(92) predicts a decrease in ET rate of at least two orders of magnitude, whereas the standard Pathways analysis predicts no change in ET rate since ET via Met(98) is not affected. Experimentally, the ET rates of the Y30I and Y30F mutants were indistinguishable from that of wild-type amicyanin. Likely explanations for these observations are discussed as are their implications for predicting pathways for ET reactions of metalloproteins.

Algorithms↗
PubMed1998

Comparative analysis of L-DOPA actions on nociceptive and non-nociceptive spinal reflex pathways in the cat.

The actions of L-DOPA (40-100 mg/kg i.v.) on nociceptive and non-nociceptive spinal reflex pathways were investigated in anaemically decapitated high spinal cats. The results revealed a differential pattern of effects of L-DOPA on monosynaptic and oligo-orpolysynaptic nociceptive and non-nociceptive reflexes. (1) L-DOPA depressed monosynaptic reflexes of flexors without affecting those of the extensors. (2) Excitatory pathways from flexor reflex afferents (FRA) were distinctly depressed by L-DOPA, pathways from group II muscle afferents reacted with greater sensitivity than pathways from non-nociceptive cutaneous and joint afferents. (3) Inhibitory FRA pathways were distinctly less affected by L-DOPA than excitatory ones. (4) Transmission in nociceptive excitatory FRA pathways was depressed to the same high degree as that in pathways from group II muscle afferents. (5) Effects on transmission in non-FRA pathways such as the group Ib inhibitory pathway and the excitatory nociceptive pathway from the foot pad to plantaris and intrinsic foot extensors were either minor or absent. (6) L-DOPA increased the delay in the reaction to noxious stimulation. (7) The effects of L-DOPA could not be specifically antagonised by naloxone. Thus, mainly excitatory FRA pathways, irrespective of a nociceptive or non-nociceptive origin, are under strong depressive dopaminergic influences. These effects are similar to those evoked by opioids.

Animals↗
PubMed1984

Evaluation of a new defibrillation pathway: tongue-epigastric/tongue-apex route. II. Impedance characteristics in human subjects.

An automated device for defibrillation using a vertical shock pathway (tongue-epigastric or tongue-apex) has been developed. The energy requirements for defibrillation using vertical pathways are uncertain and will be determined largely by the impedance of the pathway. The purpose of this study was to determine the impedance characteristics of vertical defibrillation pathways in human subjects. Twenty patients undergoing elective cardioversion of atrial fibrillation or atrial flutter, or both, were studied. Patients received shocks from electrodes placed in tongue-epigastric or tongue-cardiac apex positions. The tongue electrode was a 12 cm2 metal plate fixed to a standard plastic oropharyngeal airway. The epigastric or cardiac apex electrode was a 40 cm2 self-adhesive pad. The electrodes were connected to a standard damped-sinusoidal waveform defibrillator. It was found that the two vertical shock pathways had substantially higher impedance than the standard transthoracic pathway: tongue-epigastric pathway 130 +/- 11 omega (SD), tongue-apex pathway 115 +/- 12 omega, transthoracic pathway 68 +/- 11 omega (p less than 0.05). The higher impedance is probably due to the longer interelectrode distances of vertical pathways: tongue-epigastric 33 +/- 3 cm, tongue-apex 28 +/- 3 cm, transthoracic 23 +/- 3 cm (p less than 0.05). Vertical pathway shocks were successful in the cardioversion of 15 of 20 patients. Four of the five patients in whom vertical shocks were unsuccessful subsequently underwent successful cardioversion by transthoracic shocks; the transthoracic shocks achieved a higher current because of lower impedance of the transthoracic route.(ABSTRACT TRUNCATED AT 250 WORDS)

Abdomen↗
PubMed1999

Catheter-induced mechanical trauma to accessory pathways during radiofrequency ablation: incidence, predictors and clinical implications.

OBJECTIVES: To evaluate the incidence, predictors and clinical implications of nonintentionally catheter-induced mechanical trauma to accessory pathways during radiofrequency ablation procedures. BACKGROUND: Data on the incidence and significance of catheter-induced trauma to accessory pathways are scarce. METHODS: Consecutive patients (n = 381) undergoing radiofrequency ablation of accessory pathways at two different institutions were closely monitored for appearance of mechanical block of accessory pathways during catheter manipulation. RESULTS: Mechanical trauma to accessory pathways was observed in 37 (9.7%) patients. According to a multivariate analysis, the only independent variable associated with this phenomenon was the anatomical pathway location (p = 0.0001). The incidence of trauma of either right anteroseptal (38.5%) or right atriofascicular pathways (33.3%) was significantly greater than that of pathways (< or =10%) at all remaining locations (p < 0.0001). The duration of conduction block observed ranged from < or =1 min to >30 min in 19% and 35% of patients, respectively. "Immediate" application of radiofrequency pulses at sites of mechanical block (<1 min after occurrence) was associated with a 78% long-term success rate at follow-up. This contrasted with a 25% long-term success rate in patients in whom pulses were delivered 30 min after occurrence of block ("delayed pulses"). Finally, in 24% of patients persistent trauma-induced conduction block led to discontinuation of the ablation procedure. CONCLUSIONS: Trauma to accessory pathways is more common than previously recognized and frequently results in prolongation or discontinuation of the ablation procedure and in lower success rates. The only independent predictor of catheter-trauma to accessory pathways is the pathway location.

Adolescent↗
PubMed2000

Improved outcomes for hospitalized asthmatic children using a clinical pathway.

BACKGROUND: Although asthma clinical pathways are used with increasing frequency, few controlled studies have evaluated the clinical and cost effectiveness of these pathways. OBJECTIVE: To evaluate the effect of an inpatient asthma clinical pathway on cost and quality of care for children with asthma. METHODS: One hundred forty-nine children were treated for status asthmaticus using an asthma clinical pathway in a children's hospital between September and December 1997. Thirty-four of 149 children treated with the clinical pathway were randomly selected. A retrospective cohort control group of non-pathway patients (N = 34) was matched with each pathway patient by age, race, gender, co-morbidities, asthma severity score, ICU admission, and time of year admitted. Differences between the two groups in length of stay, total costs, readmission rate, inpatient management, and discharge medications were compared. RESULTS: Length of stay was significantly lower in the clinical pathway group compared with the control group (36 hours versus 71 hours, P < .001) and total costs decreased significantly ($1685 versus $2829, P < .001) as a result of the pathway. Asthmatic children on the clinical pathway were significantly more likely than the control group to complete asthma teaching while hospitalized (65% versus 18%, P < .001), to be discharged with a prescription for a controller medication (88% versus 53%, P < .01), and to have a peak flow meter (57% versus 23%, P < .05) and a spacer device (100% versus 71%, P < .001) for home use. CONCLUSION: Implementation of this inpatient clinical pathway led to a decrease in length of stay and a reduction in total cost while improving quality of care for hospitalized asthmatic children.

Asthma↗
PubMed2003

Fluid flow shear stress stimulates human osteoblast proliferation and differentiation through multiple interacting and competing signal transduction pathways.

This study sought to assess the role of several signaling pathways in the fluid flow shear stress-induced proliferation and differentiation of normal human osteoblasts. We evaluated the effects of an effective dose of selective inhibitors of the extracellular signal-regulated kinases (ERK) pathway (PD98059 and U0126), the nitric oxide synthase pathway (N(omega)-nitro-L-arginine methyl ester), the cyclo-oxygenase pathway (indomethacin), or the Gi/o pathway (pertussis toxin [PTX]) on the flow-mediated effects. A 30-min steady flow shear stress at 20 dynes/cm(2) increased significantly [(3)H]thymidine incorporation (an indicator of proliferation), alkaline phosphatase activity (an index of osteoblast differentiation), phosphorylation of ERK, and expression of integrin beta1. PD98059, U0126, and N(omega)-nitro-L-arginine methyl ester completely blocked the shear stress-induced increases in ERK phosphorylation, [(3)H]thymidine incorporation, and alkaline phosphatase, but without an effect on integrin beta1 expression, indicating that the ERK and nitric oxide synthase pathways are essential for the shear stress-induced proliferation and differentiation of normal human osteoblasts and that each involves ERK activation but not integrin beta1 upregulation. Indomethacin blocked the shear stress-induced osteoblast proliferation and differentiation and integrin beta1 upregulation but not ERK activation, suggesting that the cyclo-oxygenase pathway (i.e., prostacyclin and/or prostaglandin E(2)) mediates the shear stress-induced osteoblast proliferation in an ERK-independent manner. In contrast, PTX completely blocked the flow-induced increase in integrin beta1 expression but had no effect on the increase in the ERK phosphorylation or [(3)H]thymidine incorporation. PTX not only did not inhibit but also significantly enhanced the stimulatory effect of shear stress on alkaline phosphatase activity, suggesting that a PTX-sensitive signaling pathway may have an inhibitory role in osteoblast differentiation. In summary, this study shows, for the first time, that the signal transduction mechanism of shear stress in osteoblasts is complex and involves multiple ERK-dependent and independent pathways, and provides circumstantial evidence that there may be a PTX-sensitive pathway that has completing effects with an unknown pathway on the differentiation of normal human osteoblasts.

Alkaline Phosphatase↗
PubMedDate not supplied

Unique functional properties of the APB sensitive and insensitive rod pathways signaling light decrements in mouse retinal ganglion cells.

Light decrements are mediated by two distinct groups of rod pathways in the dark-adapted retina that can be differentiated on the basis of their sensitivity to the glutamate agonist DL-2-amino-phosphonobutyric (APB). By means of the APB sensitive pathway, rods transmit light decrements via rod bipolar cells to AII amacrine cells, then to Off cone bipolar cells, which in turn innervate the dendrites of Off ganglion cells. APB hyperpolarizes rod bipolar cells, thus blocking this rod pathway. With APB insensitive pathways, rods either directly synapse onto Off cone bipolar cells, or rods pass light decrement signal to cones by gap junctions. In the present study, whole-cell patch-clamp recordings were made from ganglion cells in the dark-adapted mouse retina to investigate the functional properties of APB sensitive and insensitive rod pathways. The results revealed several clear-cut differences between the APB sensitive and APB insensitive rod pathways. The latency of Off responses to a flashing spot of light was significantly shorter for the APB insensitive pathways than those for the APB sensitive pathway. Moreover, Off responses of the APB insensitive pathways were found to be capable of following substantially higher stimulus frequencies. Nitric oxide was found to selectively block Off responses in the APB sensitive rod pathway. Collectively, these results provide evidence that the APB sensitive and insensitive rod pathways can convey different types of information signaling light decrements in the dark-adapted retina.

Aminobutyrates↗
PubMed2003

Two pathways of activation of the superoxide-generating NADPH oxidase of phagocytes in vitro--distinctive effects of inhibitors.

The NADPH oxidase complex of phagocytes comprises a membrane-associated flavocytochrome b559, and 4 cytosolic components: p47phox, p67phox, p40phox, and the small GTPase Rac. Activation of the oxidase in vivo is the result of assembly of the cytosolic components with cytochrome b559 and is mimicked in vitro by a cell-free system consisting of membranes, p47phox, p67phox, nonprenylated or prenylated Rac, and an anionic amphiphile as activator (defined as "p47phox and amphiphile-dependent" or canonical pathway). We reported that prenylated Rac1 is capable of activating the NADPH oxidase in vitro in the absence of p47phox and amphiphile (defined as "p47phox and amphiphile-independent" pathway). We now demonstrate that the 2 pathways exhibit distinctive susceptibilities to inhibitors: 1) The anionic amphiphile lithium dodecyl sulfate, an activator of the canonical pathway, has the opposite effect (inhibition) on oxidase activation by prenylated Rac and p67phox; 2) GDP and, paradoxically, GTP (but not GMP, ATP, ADP, and AMP) prevent oxidase activation by the p47phox and amphiphile-independent pathway but do not affect activation by the canonical pathway; 3) The Rac-binding domain of p21-activated kinase is a potent inhibitor of activation by the p47phox and amphiphile-independent pathway while exerting a milder inhibitory effect on the canonical pathway; 4) The C-terminal polybasic Rac1 peptide 177-191 and the cationic antibiotic neomycin sulfate inhibit activation by the canonical pathway but do not affect activation by the p47phox and amphiphile-independent pathway; 5) Binding of prenylated Rac1 to membrane-mimicking phospholipid vesicles is, nevertheless, enhanced when these contain negatively charged lipids. It is proposed that preferential inhibition of oxidase activation, via the p47phox and amphiphile-independent pathway, is a reflection of interference by the inhibitors with Rac-dependent recruitment of p67phox to the membrane.

Animals↗