Initial Negative Deflection Research Articles

Torsion balance helps identify ferro-, dia- and paramagnetic materials

A neodymium magnet mounted on a torsion balance was placed near samples of ferro- dia- and paramagnetic material held in a plastic container. Similar experiments have used a cotton thread (with no restoring torque) and a pencil as the balance to allow students/pupils to detect the magnetization of many household commodities such as water, Blue-tac, fruit and salt. The present work uses a metallic wire as a suspension which provides a restoring torque due to the elasticity in the wire. Thus, a measurable deflection can be observed when the magnetic and torsion forces balance. For aluminium, the initial negative deflection is a manifestation of Lenz’s law.

The Rise Slope of the Compound Sensory Nerve Action Potential in Normal and Pathological Human Nerves

ABSTRACT In spite of the diagnostic importance of the early phase of the sensory nerve action potential (SNAP), reliable electrodiagnostic metrics for this part of the recorded waveform are lacking. The average rise slope of the SNAP appreciates the steepness of the initial negative deflection of the waveform, which might be a useful metric for the first part of the potential. Sural nerve sensory neurography was performed in patients with various axonal neuropathies, and median nerve sensory studies were carried out in patients with carpal tunnel syndrome. Age-matched healthy individuals served as controls. The rise slope was compared to conventional SNAP parameters such as conduction velocity, latency, duration, and rise time. Overall, 537 sensory studies were prospectively analyzed. The rise slope of the sural SNAP demonstrated superior classification performance in terms of sensitivity (92.5%), specificity (97%), and area under the receiver operating characteristic curve (0.986), as compared to conventional SNAP parameters. Its diagnostic power was similarly excellent in median nerve studies, whereas here a slightly better classification performance was obtained by SNAP latency and conduction velocity. The average rise slope appears to do justice to the tight interplay between amplitude and rise time of the initial negative spike deflection, outperforming many conventional measures. This composite metric proved high diagnostic potency in particular with regard to axonal sensory nerve dysfunction.

PO-05-147 RIGHT ON Q: WIDE-COMPLEX TACHYCARDIA IN SETTING OF DEXTROPOSITION

Dextroposition is a rare cardiac malformation defined as rightward cardiac displacement with leftward apex, vs. dextrocardia, which is rightward base-axis orientation. We report the second known case of dextroposition with accessory pathway, presenting as preexcited atrial tachycardia. Abnormal anatomy complicates ECG localization and pathway ablation. N/A N/A A 50-year-old woman was admitted with respiratory distress due to EBV infection. Chest X-ray showed right-sided heart. A month later, she presented in wide-complex tachycardia, rate 205 bpm. She was cardioverted after minimal response to procainamide/adenosine. Post-cardioversion ECG showed short PR interval and preexcitation, confirming presence of accessory pathway. However, the wide-complex tachycardia had morphology identical to baseline, supporting preexcited atrial tachycardia over AVRT. Despite X-ray findings and reverse R-wave progression in precordial leads, presence of left axis deviation and initial negative deflection in aVR argued against dextrocardia. Moreover, aVR had negative T- and P-waves, findings associated with levocardia. Thus, dextroposition was suspected. Millstein and Arruda criteria suggested posteroseptal accessory pathway, but no data on their applicability in right-sided heart exist. EP study was performed. Eccentric VA conduction was noted. Earliest activation was at proximal coronary sinus. During isoproterenol infusion, patient went into atrial tachycardia, cycle length 420ms. Multiple AT foci were identified, including at right atrial appendage and tricuspid annulus. During ablation, patient developed atrial fibrillation with preexcited RR <250ms, confirming high-risk accessory pathway. Given numerous AT foci and high risk, it was decided to focus on pathway over tachycardia sites. Pathway was successfully ablated at ostia of coronary sinus and middle cardiac vein. One prior case of accessory pathway ablation in dextroposition has been reported. This patient had left lateral pathway and multiple congenital abnormalities including lung hypoplasia. While our patient was found to have multifocal atrial tachycardia, she had no clinical or radiographic lung disease. ECG changes in dextroposition are less predictable than in dextrocardia; they vary with cardiac rotation, axis position, and lead position. Comorbid accessory pathway is rare; ECG-anatomy relationship is ill-defined. Structural abnormalities pose individual challenges during electrophysiologic procedures.

P-Wave Morphology in Focal Atrial Tachycardia: An Updated Algorithm to Predict Site of Origin.

This study sought to report P-wave morphology (PWM) from a series of paraseptal (PS) atrial tachycardia (AT), revise then prospectively evaluate a simplified PWM algorithm against a contemporary consecutive cohort with focal AT. The 2006 PWM algorithm was useful in predicting the origin of focal AT. An updated algorithm was developed given advances in multipolar 3-dimensional mapping, potential limitations of PWM in separating PS sites, and a renewed interest in the P-wave in mapping non-pulmonary vein triggers. The PWM from a consecutive series of 67 patients with PS AT were analyzed. PS sites included were coronary sinus ostium, perinodal, left and right septum, septal tricuspid annulus, superior mitral annulus, and noncoronary cusp. Next the P-wave algorithm was revised and prospectively evaluated by 3 blinded assessors. The P-wave for PS sites was neg/pos (n= 50), iso/pos (n= 10), or isoelectric (n= 4) in lead V1 (96%). The P-wave algorithm was modified and prospectively applied to 30 consecutive patients with focal AT who underwent successful ablation. Foci (n=30) originated from the right atrium (33.3%), left atrium (30%), and PS (36.7%). Using the PW algorithm, the correct anatomic location was identified in 93%. Incorrect interpretation of the terminal positive P-wave component (n=3) and initial negative P-wave deflection (n=1) in lead V1 misidentified 4 paraseptal cases. The revised PWM algorithm offers a simplified and accurate method of localizing the responsible site for focal AT. The P-wave remains an important first step in mapping atrial arrhythmias.

Effect of locomotion on the auditory steady state response of head-fixed mice

Objectives Electroencephalographic (EEG) examinations of the auditory steady-state response (ASSR) can non-invasively probe cortical function to generate the gamma-band (40 Hz) oscillation, which is increasingly applied to the neurophysiological studies on the rodent models of psychiatric disorders. Though, it has been well established that the brain activities are significantly modulated by the behavioural state (such as locomotion), how the ASSR is affected remains unclear. Methods We investigated the effect of locomotion by recording local field potential (LFP) evoked by 40-Hz click-train from multiple brain areas: auditory cortex (AC), medial geniculate body (MGB), hippocampus (HP) and prefrontal cortex (PFC), in head-fixed mice free to run on a treadmill. Comparisons were conducted on the LFPs during spontaneous movement and stationary conditions. Results We found that in both the auditory (AC and MGB) and non-auditory areas (HP and PFC), locomotion reduced the initial negative deflection of LFP (early response during 0–100 ms from stimulus onset), and had no significant effect on the ASSR phase-locking to the late stimulus (100–500 ms). Conclusions Our results suggest that different neural mechanisms contribute to the early response and ASSR, and the ASSR is a more robust biomarker to investigate the pathogenesis of neuropsychiatric disorders.

Notched QRS for the assessment of myocardial fibrosis in hypertrophic cardiomyopathy.

Patients with hypertrophic cardiomyopathy (HCM) sometimes develop myocardial fibrosis in association with adverse cardiovascular events. Electrocardiography (ECG) could provide helpful information on myocardial fibrosis in HCM, as in coronary artery disease. A total of 60 patients with HCM without bundle branch block underwent cardiac magnetic resonance imaging (CMR). The extent or location of late gadolinium enhancement (LGE) was examined in relation to 12-lead ECG. A notch on QRS was defined as at least 2 consecutive spikes in the same polarity with a reversal of direction ≥90° and the initial negative deflection ≥0.05 mV. LGE was associated with notched QRS, leftward QRS axis, and prolonged QRS duration, but not with any other findings such as abnormal Q waves, R-wave amplitude, or ST-T changes. Notched QRS was most useful in determining the presence or absence of myocardial fibrosis, with a sensitivity of 70% and a specificity of 81% using a cut-off of the number of leads with notched QRS ≥2. The number of notched QRS leads was positively correlated with LGE volume (P<0.01) and the lead distribution of notched QRS was informative about the location of LGE. A notch on QRS was useful in estimating myocardial fibrosis as assessed on CMR LGE in HCM patients without bundle branch block.

Temporospatial dissociation of Pe subcomponents for perceived and unperceived errors

Previous research on performance monitoring revealed that errors are followed by an initial fronto-central negative deflection (error-related negativity, ERN or Ne) and a subsequent centro-parietal positivity (error positivity, Pe). It has been shown that error awareness mainly influences the Pe, whereas the ERN seems unaffected by conscious awareness of an error. The aim of the present study was to investigate the relation of ERN and Pe to error awareness in a visual size discrimination task in which errors are not elicited by impulsive responding but by perceptual difficulty. Further, we applied a temporospatial principal component analysis (PCA) to examine whether the temporospatial subcomponents of the Pe would differentially relate to error awareness. Event-related potential (ERP) results were in accordance with earlier studies: a significant error awareness effect was found for the Pe, but not for the ERN. Interestingly, a modulation with error perception on correct trials was found: correct responses considered as incorrect had larger correct-related negativity (CRN) and lager Pe amplitudes than correct responses considered as correct. The PCA yielded two relevant spatial factors accounting for the Pe (latency 300 ms). A temporospatial factor characterized by a centro-parietal positivity varied significantly with error awareness. Of the two temporospatial factors corresponding to ERN and CRN, one factor with central topography varied with response correctness and subjective error perception on correct responses. The PCA results indicate that the error awareness effect is specifically related to the centro-parietal subcomponent of the Pe. Since this component has also been shown to be related to the importance of an error, the present variation with error awareness indicates that this component is sensitive to the salience of an error and that salience secondarily may trigger error awareness.

Sweat production and the sympathetic skin response: Improving the clinical assessment of autonomic function

The aim of this project was to establish the relationship between sweat production and the electrodermal events comprising the sympathetic skin response to arousal stimuli. A series of randomly timed magnetic stimuli were applied to the neck of healthy human volunteers. Sympathetic skin responses and the associated sweat responses were recorded from the palms of both hands. Sympathetic skin responses typically had a biphasic shape consisting of a negative initial potential (palm relative to dorsum of hand) followed by a positive deflection. Sweat production was positively correlated with amplitude of the second positive deflection of the sympathetic skin response and negatively correlated with the amplitude of the initial negative deflection. For subjects showing only an initial negative sympathetic skin response, sweat release was low or not detectable. During habituation, the negative initial wave increased relative to the second positive wave, and sweat production fell. The strong correlation between the positive wave of the sympathetic skin response and sweat production suggests that the former may provide a quantitative functional measure of sudomotor activity in situations when it is impractical to measure the amount of sweat produced in the startle response. Thus, the positive component of the biphasic sympathetic skin response may be employed in clinical assessment of the functional efficacy of the sympathetic sudomotor system.

Acoustic hypersensitivity in adult rats after neonatal ventral hippocampus lesions

Rats with a bilateral neonatal ventral hippocampus lesion (NVHL) are used as models of neurobiological aspects of schizophrenia. In view of their decreased number of GABAergic interneurons, we hypothesized that they would show increased reactivity to acoustic stimuli. We systematically characterized the acoustic reactivity of NVHL rats and sham operated controls. They were behaviourally observed during a loud white noise. A first cohort of 7 months’ old rats was studied. Then the observations were reproduced in a second cohort of the same age after characterizing the reactivity of the same rats to dopaminergic drugs. A third cohort of rats was studied at 2, 3, 4, 5 and 6 months. In subsets of lesioned and control rats, inferior colliculus auditory evoked potentials were recorded. A significant proportion of rats (50–62%) showed aberrant audiogenic responses with explosive wild running resembling the initial phase of audiogenic seizures. This was not correlated with their well-known enhanced reactivity to dopaminergic drugs. The proportion of rats showing this strong reaction increased with rats’ age. After the cessation of the noise, NVHL rats showed a long freezing period that did neither depend on the size of the lesion nor on the rats’ age. The initial negative deflection of the auditory evoked potential was enhanced in the inferior colliculus of only NVHL rats that displayed wild running. Complementary anatomical investigations using X-ray scans in the living animal, and alizarin red staining of brain slices, revealed a thin layer of calcium deposit close to the medial geniculate nuclei in post-NVHL rats, raising the possibility that this may contribute to the hyper-reactivity to sounds seen in these animals. The findings of this study provide complementary information with potential relevance for the hyper-reactivity noted in patients with schizophrenia, and therefore a tool to investigate the underlying biology of this endophenotype.

Effect of High-Dose Intracoronary Adenosine Administration During Primary Percutaneous Coronary Intervention in Acute Myocardial Infarction: A Randomized Controlled Trial

Effect of High-Dose Intracoronary Adenosine Administration During Primary Percutaneous Coronary Intervention in Acute Myocardial Infarction: A Randomized Controlled Trial

Model-based source localization of extracellular action potentials

A new model-based analysis method was set up for revealing information encrypted in extracellular spatial potential patterns of neocortical action potentials. Spikes were measured by extracellular linear multiple microelectrode in vivo cat’s primary auditory cortex and were analyzed based on current source density (CSD) distribution models. Validity of the monopole and other point source approximations were tested on the measured potential patterns by numerical fitting. We have found, that point source models could not provide accurate description of the measured patterns. We introduced a new model of the CSD distribution on a spiking cell, called counter-current model (CCM). This new model was shown to provide better description of the spatial current distribution of the cell during the initial negative deflection of the extracellular action potential, from the onset of the spike to the negative peak. The new model was tested on simulated extracellular potentials. We proved numerically, that all the parameters of the model could be determined accurately based on measurements. Thus, fitting of the CCM allowed extraction of these parameters from the measurements. Due to model fitting, CSD could be calculated with much higher accuracy as done with the traditional method because distance dependence of the spatial potential patterns was explicitly taken into consideration in our method. Average CSD distribution of the neocortical action potentials was calculated and spatial decay constant of the dendritic trees was determined by applying our new method.

Influence of high-pass filtering on noncontact mapping and ablation of atrial tachycardias.

The aim of the study was to define the impact of different high-pass filter settings (HPF) on the accuracy of mapping of ectopic atrial tachycardias (EAT) using a noncontact mapping (NCM) system. In 20 patients with 22 EAT a noncontact probe was deployed in the right (n = 19) or in the left atrium (n = 3). The device enables interpolation and analysis of unipolar electrograms. It provides information on focus localization and signal morphology. These parameters were compared in different HPF of 0.5 Hz, 2 Hz, 8 Hz, and 16 Hz. The NCM signal morphology was preserved at all HPF. An initial negative deflection recorded by NCM system showed a positive predictive value of 93% regarding the ablation success. The deviation (spatial disparity) between visualized focus origin and successful ablation site was 6.9 +/- 5.4 mm. Between two consecutive filter settings, the focus shift was more pronounced between 0.5 and 2 Hz (5.4 +/- 4.5 mm) compared to a setting between 8 and 16 Hz (2.9 +/- 2.9 mm; P < 0.05). Successful ablation was achieved in 15/18 right atrial tachycardias (83%) and in 2/3 left atrial arrhythmias. Different HPF influence NCM spatial analysis of EAT. However, a small variability in foci localization does not impact final ablation results.

Focal atrial tachycardia arising from the tricuspid annulus: electrophysiologic and electrocardiographic characteristics.

Focal right atrial tachycardia (RAT) arising from the crista terminalis, para-Hisian, and coronary sinus os regions are well described. Less information exists regarding RAT arising from the nonseptal region of the tricuspid annulus (TA). From a consecutive series of 64 patients who had undergone successful radiofrequency ablation (RFA) of 67 RATs, the characteristics of 9 (13%) patients (6 men; mean age 50 +/- 20 years) with a TA focus were reviewed. The annular focus was localized to the inferoanterior TA in 7 and the superior TA in 2. Mean tachycardia cycle length was 371 +/- 66 msec. Mean activation time at the site of successful RFA in 9 of 9 patients was -43 +/- 11 msec. At 9.3 +/- 5.6 months of follow-up, 1 of 9 patients had recurrent tachycardia successfully treated with repeat RFA. In 7 of 9 patients with RAT from the inferoanterior TA, the surface ECG P wave morphology was upright in aVL, inverted in III and VI, and either inverted or biphasic with an initial negative deflection from V2 to V6. The TA is an important site of origin of RAT. In the present study, the inferoanterior region of the TA was a preferential site of origin with resulting characteristic P wave morphology. Knowledge of this anatomic distribution and P wave morphology allows targeted mapping and may facilitate successful RFA.

COMPARISON OF THREE METHODS FOR RECORDING TIBIAL H REFLEX

Recording the tibial H reflex from the calf is routine in clinical electromyography. Two widely used methods are Hugon's and Braddom and Johnson's. Both methods produce an H wave with an initial positive deflection. Another method, the "half and half" method, generates an H wave with an initial negative deflection. To compare these methods, H-reflex responses were recorded in the right calf of 20 normal adults with each method using identical amplifier and stimulator settings. Stimulus current was increased by increments of 0.5-1.0 mA until the H reflex and motor (M) wave responses reached maximum amplitudes (Hmax, Mmax). H wave to M wave (H/M) amplitude ratios were calculated. The half-and-half method produced greatest Hmax, Mmax, and H/M ratio. Wave form configuration for the half-and-half method was biphasic with an initial negative deflection; it was triphasic with an initial positive deflection with the other methods. The shapes of M and H waves were similar in two methods but dissimilar in one. Because of the greater amplitude and the initial negative deflection, the H wave may be easier to detect with the half-and-half method and may present a latency that is more easily determined. For these reasons, the half-and-half method is recommended for measuring amplitude and latency in clinical settings.

On the selection of concentric needle electromyogram motor unit action potentials: is the rise time criterion too restrictive?

Concentric needle electromyogram motor unit action potentials (MUAPs) were recorded from the biceps brachii muscle of normal subjects and in patients with neuromuscular diseases. Although the MUAPs had a crisp sound and appeared sharp, their rise time (RT), measured from the maximum negative peak to the preceding maximum positive peak before it, was often > 500 microseconds. All MUAPs with a RT < or = 500 microseconds were recorded from within the motor unit (MU) territory. MUAP recordings from outside the MU territory had a long RT but also low amplitude (< 50 microV) and/or a characteristic initial negative deflection. In the remaining recordings from within the MU territory, MUAP duration remained relatively constant while MUAP amplitude and RT varied inversely with each other. These MUAPs may be useful in electrodiagnosis but discarded due to their longer RT. We feel that while the current RT criterion for MUAP selection ensures that the electrode tip is within the MU territory, it is also too restrictive.

Effects of long-term oral administration of amiodarone on the ventricular repolarization of rabbit hearts.

The chronic effects of amiodarone on ventricular repolarization were investigated in Langendorff-perfused rabbit hearts in comparison with the acute effects of other Class III antiarrhythmic drugs. Forty to fifty electrograms were recorded through modified bipolar electrodes from the anterior to the lateral epicardial surface of the ventricles under His-bundle pacing (1.0 Hz). In control hearts, epicardial activation proceeded from the apex to the base. The interval from the initial sharp negative deflection of the QRS complex to the apex of the T-wave (Q-aT), which reflects the action potential duration (APD) at the recording site, was longest in the apex and shortest in the base. Therefore, repolarization proceeded from the base to the apex. In hearts treated with oral amiodarone (100 mg/kg, 4 weeks), Q-aT was uniformly prolonged by 14-16% throughout the entire mapped area, whereas the activation sequence was unaffected, and a normal Q-aT gradient was well preserved from the apex to the base. The spatial inhomogeneity of left ventricular repolarization was not enhanced by drug treatment. Acute application of sotalol (30 mumol/L), E-4031 (0.1 mumol/L) or MS-551 (1.0 mumol/L) caused a much greater Q-aT prolongation in the apex than in the base, resulting in a marked enhancement of the spatial inhomogeneity of repolarization. These findings suggest that the propensity of chronic amiodarone to induce torsade de pointes less often than other Class III agents may result at least in part from its favorable effect on the spatial homogeneity of ventricular repolarization.

901–47 New Criteria for the Diagnosis of Inferior Infarction in Patients with Left Bundle Branch Block

The ability to diagnose inferior infarction in patients with left bundle branch block (LBBB) is limited by the lack of established criteria. To develop criteria, the ECGs of 187 patients with LBBB who had either normal results (Normals) or an isolated, unequivocal inferior infarct (IMI) on stress thallium testing were examined. Patients with acute IMI within 30 days of the thallium were excluded. LBBB was defined as DRS duration ≥ 120 msec with the classic patterns of DRS/T changes in leads I, aVL, V5, and V6. Q-waves were significant if they were ≥ 30 msec in duration and 25% the height of the R-wave; T-waves were considered inverted if they were either totally negative or biphasic with initial negative deflection. The presence of diagnostic Q-waves or T-inversion in aVF was found to be predictive of IMI in patients with LBBB with 85% sensitivity and 86% specificity. The presence of both Q-waves and T-inversion in aVF was diagnostic with a specificity of 100% though a low sensitivity of 13%. Finding Sensitivity Specificity Q 15/39 (38%) 143/148 (97%) T↓ 23/39 (59%) 133/148 (90%) Q or T 33/39 (85%) 128/148 (86%) Q or T↓ 5/39 (13%) 148/148/(100%) The presence of either a Q-wave or T-inversion in aVF appears to be useful in predicting past inferior infarction in patients with LBBB. The combination of the two, though rare, has a high positive predictive value.

Physiological study of cervical dystonia. Task-specific abnormality in contingent negative variation.

To investigate the pathophysiology of dystonia, we recorded contingent negative variation (CNV) in 12 patients with cervical dystonia and in 12 age-matched normal subjects. In a simple reaction time paradigm, the subjects were given a pair of a warning stimulus and a subsequent stimulus that triggered head rotation to either side or extension of the fingers. In normal subjects, CNVs for head rotation were not affected by neck muscle pre-activation simulating torticollis, and were always symmetrical with equally high amplitudes over the frontal and central leads. By contrast, CNVs for finger movement had the maximum over the central lead and showed a characteristic distribution; those for the right finger movement had the left hemisphere dominance, whereas those for the left finger movement had similar amplitudes over both hemispheres. In patients with rotatory torticollis (rotatocollis), the components of CNVs for head rotation were markedly attenuated in all the leads, except for the initial negative deflection (orienting response). As a whole, cervical dystonia patients had significantly lower amplitudes of late CNVs for head rotation than normal subjects (P < 0.001), whereas late CNV amplitudes in finger extension did not differ in the two groups. Their reaction times for head rotation were similar, but durations of EMG activities were prolonged in the patients because of co-contractions of the antagonists. The task-specific CNV amplitude loss is therefore not explained by reaction times or by the abnormal neck muscle activities prior to the movement, but it reflects a failure of neural activities preparing for a phasic neck movement, resulting in co-contraction of the agonists and the antagonist. Dystonia may be associated with defective retrieval or retaining of specific motor programmes or subroutines in response to sensory stimuli.

Sympathetic skin response--physiologic principles, normal values and clinical use

Sympathetic skin reflex (SSR) was evaluated in the lower extremities of 60 normal volunteers aged 17 to 72 (mean age 38 +/- 16 years, 28 females, 32 males). SSR was obtainable in all volunteers and most often consisted of a biphasic wave with initial negative deflection. Mean latency was 2.16 +/- 0.20 s. Mean variation in a second repetitive measurement was 0.21 +/- 0.14 s. The SSR was not age- or sex dependent. There was a weak positive correlation of the SSR with the height of the volunteers (r = 0.271; p = 0.037). SSR was investigated in 39 patients with polyneuropathy (age 59 +/- 18). SSR was pathological in 51% on one or both legs. There was no correlation of the SSR to the aetiology nor to the type of lesion (axonal versus demyelinating polyneuropathy) nor to clinical symptoms. The applicability of the SSR is reviewed from the literature regarding polyneuropathy, erectile dysfunction, central degenerative diseases, multiple sclerosis, sympathetic reflex dystrophies, spinal and peripheral nerve lesions. SSR is briefly compared to alternative methods. SSR appears to be a reasonable method to describe a small section of the autonomic nervous system (sympathetic sudomotor function) and to calculate group differences. There appears to be no close correlation to any of the autonomic disturbances in individual patients.

Effects of prostaglandin E2 on membrane voltage of the connecting tubule and cortical collecting duct from rabbits.

1. Effects of prostaglandin E2 (PGE2) on ion transport were examined by observing the transmural (VT) and basolateral membrane voltage (VB) in the in vitro perfused rabbit connecting tubule (CNT) and the cortical collecting duct (CCD). 2. Addition of 1 microM PGE2 to the bath induced a biphasic response of transmural voltage (VT), with initial negative VT deflection followed by positive deflection in the CNT, but monophasic negative deflection in the CCD. Because PGE2 had no affect on the basolateral membrane voltage (VB), PGE2 mainly causes changes in the apical membrane voltage. 3. Elimination of Na+ from the lumen abolished the PGE2-induced VT response in the CNT. In the presence of 10 microM luminal amiloride, PGE2 caused only an initial negative deflection without causing later positive deflection. The positive VT deflection induced by PGE2 in the CCD was also blocked by luminal amiloride. 4. Addition of ouabain (0.1 mM) to the bath completely abolished the PGE2-induced VT changes in the CNT, indicating that an intact Na(+)-K+ pump is a prerequisite for the VT response to PGE2. 5. Addition of 2 mM Ba2+ to the lumen did not affect biphasic VT response to PGE2, indicating that Ba(2+)-sensitive K+ conductance is not involved. 6. Basolateral addition of 0.1 mM 8-(4-chlorophenylthio)-cAMP inhibited only the negative VT deflection induced by PGE2. 7. The positive VT deflection was blocked by basolateral addition of 50 microM 8-(N,N-diethylamino)octyl 3,4,5-trimethoxy benzoate hydrochloride (TMB-8), an inhibitor of intracellular Ca2+ release. But elimination of luminal Ca2+ did not affect the biphasic response to PGE2. 8. These findings suggest that the initial negative VT deflection is caused by an increase in Na+ influx across the luminal membrane through an amiloride-insensitive Na+ conductive pathway, whereas the later positive deflection is caused by the inhibition of Na+ influx through the amiloride-sensitive Na+ conductive pathway. The cAMP messenger system may be responsible for the initial negative deflection, whereas an increased intercellular Ca2+ release from the store is necessary for the later positive deflection caused by PGE2. The response in the CCD is comparable to the later response in the CNT.