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Biomedical subjects

M J Correia

Publications and source records attributed to M J Correia.

At least 19 recordsLinked to original sources

The delayed rectifier, IKI, is the major conductance in type I vestibular hair cells across vestibular end organs.

Hair cells were dissociated from the semicircular canal, utricle, lagena and saccule of white king pigeons. Type I hair cells were identified morphologically based on the ratios of neck width to cuticular plate width (NPR < 0.72) as well as neck width to cell body width (NBR < 0.64). The perforated patch variant of the whole-cell recording technique was used to measure electrical properties from type I hair cells. In voltage-clamp, the membrane properties of all identified type I cells were dominated by a predominantly outward potassium current, previously characterized in semicircular canal as IKI. Zero-current potential, activation, deactivation, slope conductance, pharmacologic and steady-state properties of the complex currents were not statistically different between type I hair cells of different vestibular end organs. The voltage dependence causes a significant proportion of this conductance to be active about the cell's zero-current potential. The first report of the whole-cell activation kinetics of the conductance is presented, showing a voltage dependence that could be best fit by an equation for a single exponential. Results presented here are the first data from pigeon dissociated type I hair cells from utricle, saccule and lagena suggesting that the basolateral conductances of a morphologically identified population of type I hair cells are conserved between functionally different vestibular end organs; the major conductance being a delayed rectifier characterized previously in semicircular canal hair cells as IKI.

4-Aminopyridine

Electrical filtering in gerbil isolated type I semicircular canal hair cells.

1. Membrane potential responses of dissociated gerbil type I semicircular canal hair cells to current injections in whole cell current-clamp have been measured. The input resistance of type I cells was 21.4 +/- 14.3 (SD) M omega, (n = 25). Around the zero-current potential (Vz = -66.6 +/- 9.3 mV, n = 25), pulsed current injections (from approximately -200 to 750 pA) produced only small-amplitude, pulse-like changes in membrane potential. 2. Injecting constant current to hyperpolarize the membrane to around -100 mV resulted in a approximately 10-fold increase in membrane resistance. Current pulses superimposed on this constant hyperpolarization produced larger and more complex membrane potential changes. Depolarizing currents > or = 200 pA caused a rapid transient peak voltage before a plateau. 3. Membrane voltage was able to faithfully follow sine-wave current injections around Vz over the range 1-1,000 Hz with < 25% attenuation at 1 kHz. A previously described K conductance, IKI, which is active at Vz, produces the low input resistance and frequency response. This was confirmed by pharmacologically blocking IKI. This conductance, present in type I cells but not type II hair cells, would appear to confer on type I cells a lower gain, but a much broader bandwidth at Vz, than seen in type II cells.

Animals

Functional support of glutamate as a vestibular hair cell transmitter in an amniote.

Although hair cells in the cochlea and in the vestibular endorgans of anamniotes are thought to release glutamate or a similar compound as their transmitter, there is little evidence in amniotes (which, unlike anamniotes, possess both type I and II hair cells) as to the nature of the hair cell transmitters in the vestibular labyrinth. We have recorded extracellularly from single semicircular canal afferents in the turtle labyrinth maintained in vitro and have bath-applied a number of transmitter agonists and antagonists to relate the effects of these substances to the actions of the endogenous transmitter substances. Both glutamate and aspartate strongly excite the afferents while GABA and carbachol have negligible or weak effects. In contrast to its lack of effect on afferent activity in some anamniotes, N-methyl-D-aspartate (NMDA) was also found to excite these afferents. Kynurenic acid reversibly reduced the resting firing rates of the afferents and the increases in firing due to the application of glutamate and aspartate. These findings provide preliminary support for the hypothesis that glutamate (or a related compound) is also a vestibular hair cell transmitter in amniotes.

Action Potentials

Wall motion abnormalities and late ventricular arrhythmia during the predischarge phase of acute myocardial infarction.

BACKGROUND: Left ventricular wall aneurysm is a complication of acute myocardial infarction which has been considered a precipitating factor of cardiac failure and ventricular arrhythmia. We have evaluated the relation between severe left ventricular wall motion abnormalities and ventricular arrhythmia. METHODS: During a two-year period 146 patients admitted to a coronary care unit with acute myocardial infarction were studied. Radionuclide angiography performed within the second and the fourth weeks was used to analyse phase and wall motility changes, and patients were divided into three groups: 1) Hypokinesia and/or akinesia localized to one segment: with no or slight changes in phase image--102 patients; 2) Aneurysm: left ventricular deformity with well-defined chromatic changes in phase image--19 patients; and 3) Dyskinesia and/or extensive akinesia of two or more segments: phase image with diffuse heterogeneous changes--25 patients. Ventricular arrhythmia was studied using Holter electrocardiography taken during the second week of acute myocardial infarction. Three rhythmic profiles were considered: no premature ventricular contractions--41 patients; with three or more than three premature ventricular contractions per hour--38 patients; repetitive premature ventricular contractions--20 patients. RESULTS: Premature ventricular contractions were absent in 31 (30%) of the patients with hypokinesia/localized akinesia vs 8 (42%) of the patients with aneurysm, and vs 2 (8%) of the patients with dyskinesia/extensive akinesia. Premature ventricular contractions were frequent (> or = 3/h) in 22 (22%) of the patients with hypokinesia/localized akinesia vs 4 (21%) of the patients with aneurysm (p = 0.35; NS), and vs 12 (48%) of the patients with dyskinesia/extensive akinesia (p=0.003). Repetitive premature ventricular contractions were present in 10 (10%) of the patients with hypokinesia/localized akinesia vs 2 (11%) of the patients with aneurysm, and vs 8 (32%) of the patients with dyskinesia/extensive akinesia (p=0.008). CONCLUSIONS: We conclude that the presence of aneurysm was not associated with a higher occurrence of ventricular arrhythmia, but patients with dyskinesia/extensive akinesia had a higher occurrence of ventricular arrhythmia, > or = 3 premature ventricular contractions per hour and repetitive premature ventricular contractions. Our results suggest that ventricular arrhythmia is related to functionally severe wall motion abnormalities, and not to anatomical discriminants. This finding leads us to suggest different electrophysiological mechanisms behind these two entities.

Adult

[Variability of heart rate].

AIM: The basic principles of the physiological mechanisms of heart rate variability are discussed. The different methods used in its assessment are evaluated. An overview of its clinical utility is presented. STUDY DESIGN: We reviewed the papers on this area until May 1994 we thought relevant. The more or less succinct description of their conclusions is made and commented. RESULTS: Heart rate frequency and its oscillations are regulated by the autonomic nervous system. Heart rate variability analysis is an easy non invasive means of investigating the autonomic control of the heart. There is a wealth of experimental and clinical evidence linking abnormalities of the autonomic nervous system with the development of serious ventricular arrhythmia and sudden death, and it has been clearly shown that decreased heart rate variability is associated with increased mortality in diabetes and after myocardial infarction. Abnormal heart rate variability has been detected in several other disorders such as hypertension, neurologic diseases, heart failure, renal failure, etc., although here its clinical usefulness is yet to be set. Heart rate variability is influenced by various drugs whose potential protective cardiovascular effect is under investigation. CONCLUSIONS: Heart rate variability analysis is a promising method that can be used as an index of cardiac autonomic balance and has been shown to be of significant clinical value. RR interval variation is controlled by the activity of cardiac sympathetic and parasympathetic nervous system, the function of which is influenced by many factors such as age, sex, position, breathing, hour of the day, therapeutics, etc. Different methods and results have been used by various authors. Standard values are not yet available to be used or compared in different settings. From the interest it has raised all over the world it is expected that very soon this method will have a widespread use in clinical practice, providing useful tools both for diagnostic and prognostic purposes and to monitor and guide therapeutic interventions.

Cardiovascular Diseases

Potassium currents in mammalian and avian isolated type I semicircular canal hair cells.

1. Type I vestibular hair cells were isolated from the cristae ampullares of the semicircular canals of the Mongolian gerbil (Meriones unguiculatus) and the white king pigeon (Columba livia). Dissociated type I cells were distinguished from type II hair cells by their neck to plate ratio (NPR) and their characteristic amphora shape. 2. The membrane properties of gerbil and pigeon type I hair cells were studied in whole-cell voltage- and current-clamp using the perforated patch technique with amphotericin B as the perforating agent. 3. In whole-cell current-clamp, the average zero-current potential, Vz, measured for pigeon type I hair cells, was -70 +/- 7 (SD) mV (n = 18) and -71 +/- 11 mV (n = 83) for gerbil type I hair cells. 4. At Vz, for both gerbil and pigeon type I hair cells, a potassium current (IKI) was > or = 50% activated. This current deactivated rapidly when the membrane potential was hyperpolarized below -90 mV. 5. IKI was blocked by externally applied 4-aminopyridine (4-AP) (5 mM) and by internally applied 20 mM tetraethylammonium (TEA). It was also reduced when 4 mM barium was present in the external solution. The degree of block by barium increased as the membrane potential became more positive. External cesium (5 mM) blocked the inward component of IKI. When IKI was pharmacologically blocked, Vz depolarized by approximately 40 mV. Therefore IKI appears to be a delayed rectifier and to set the more negative Vz noted for isolated type I hair cells when compared to isolated type II hair cells, which do not have IKI. 6. A second, smaller potassium current was present at membrane potential depolarizations above -40 mV. This current was blocked by 30-50 mM, externally applied TEA, 100 microM quinidine, 100 nM apamin, but not 100 nM charybdotoxin, indicating that this is a calcium-activated potassium current, IK(Ca), different from the maxi-K calcium-activated potassium current found in most other hair cells.

4-Aminopyridine

"Velocity leakage" in the pigeon vestibulo-ocular reflex.

The transfer characteristics of the vestibulo-ocular reflex (VOR), and of the semicircular canal primary afferents (SCPAs) that drive it, have been studied in several species. In monkeys and cats, the dominant time constant describing horizontal VOR dynamics (tau hv) is longer than that (tau c) of horizontal SCPAs. This lengthening of the time constant has been attributed to a "velocity storage" mechanism that has been modeled as a positive feedback loop in the VOR pathways. We have studied the transfer characteristics of horizontal and vertical VOR and SCPAs in unanesthetized pigeons. In this species the dominant time constants of both the horizontal and vertical VOR (tau hv and tau vv) are shorter that tau c. This finding indicates that time constants characterizing the lower frequency response of the VOR can be lengthened or shortened depending on the species. We propose that in the pigeon the "velocity leakage" mechanism can be modeled by substituting negative feedback for positive feedback in the model of the VOR pathways. Negative feedback can also account for the further shortening of tau hv and tau vv as VOR gain increases with arousal. Additionally, making the negative feedback loop nonlinear can model the dependency of lower frequency VOR phase on amplitude, and skew in VOR waveforms. Pigeon VOR and SCPA dynamics also differ in their adaptive properties and higher frequency behavior. A predominance of input from highly adaptive SCPAs is proposed to account for the increased adaptation of the vertical VOR as compared with SCPAs overall. A pure time-delay associated with VOR operation can explain the phase lag of the VOR relative to SCPAs at higher frequencies.

Afferent Pathways

Bilateral communication between vestibular labyrinths in pigeons.

Extracellular action potentials from single horizontal semicircular canal primary afferent fibers were recorded in paralysed decerebrate pigeons during pulse mechanical stimulation of the contralateral horizontal semicircular canal. Clear responses to the contralateral membranous duct displacement stimuli were observed in 51% of the tested 158 horizontal semicircular canal afferents. Generally, three different types of responses were obtained in the primary afferent fibers including excitation, inhibition, and a few complex type neural activity profiles. Inhibitory responses were of larger amplitude and had longer time constants than did excitatory responses. The few complex type responses observed were characterized by an initial excitatory discharge followed by a longer duration decrease in the fiber's firing rate. The sensitivity to stimulation and type of response obtained for each afferent was significantly correlated with the fiber's coefficient of variation value. Regular firing afferents were less sensitive and exhibited primarily excitatory responses (71%) to contralateral canal stimulation. Irregular firing afferents were more sensitive and exhibited mostly inhibitory responses (84%). The present results demonstrate that a communication network for information exchange between the bilateral labyrinths exists in pigeons. The observed responses in primary afferent fibers to contralateral horizontal semicircular canal stimulation are proposed to be mediated by the vestibular efferent system, which could provide an anatomical pathway for information exchange from vestibular receptors on opposite sides of the head.

Afferent Pathways

Filtering properties of hair cells.

Three questions were asked about filtering properties of hair cells. First, it was asked if hair cells in different receptors showed different filtering properties to match the receptor response to the particular characteristics of the stimulus? It seems that the answer is yes, since for example, the resonant frequencies of pigeon semicircular hair cells at membrane potentials around the RMP are in a range (12-280 Hz) that could match angular head frequencies. Since critical frequency tuning of one frequency probably is not necessary for the semicircular canals it is quite reasonable that the largest quality factor (Qe) of resonance in pigeon semicircular canal hair cells for membrane potentials around the RMP is 4 times lower than the largest Qe in bullfrog saccular hair cells and 10 times lower than Qe in the turtle basilar papilla. Second, it was asked if hair cells of the same morphological type but in different regions of the neuroepithelium have different filtering properties. It seems that this question needs more careful study since most available data on hair cells that show different filtering properties depending on their location in the neuroepithelium show subtle morphological differences and therefore the hair cells could be classified as different types. Finally, it was asked if different hair cell types (based on morphology and innervation) have different filtering properties. The currents in pigeon and guinea pig type I and type II semicircular canal hair cells, guinea pig inner and outer cochlear hair cells, goldfish short and tall saccule hair cells and chick short and tall cochlea hair cells suggest that the answer to this question is yes. The challenge is to continue to precisely specify the filtering properties of different types of hair cells in different places on the neuroepithelium of different receptors.

Animals

Aeromonas hydrophila fulminant pneumonia in a fit young man.

A previously healthy 24 year old athletic man became ill suddenly with pneumonia the day after swimming in the sea. Despite intensive support measures in the intensive care unit he died three hours after admission and 21 hours after his first symptom. Necropsy showed bilateral haemorrhagic necrotising pneumonia. Aeromonas hydrophila was isolated from a blood culture taken at admission and from the lungs at necropsy. The infection may have come from contaminated sea water.

Adult

Changes in monkey horizontal semicircular canal afferent responses after spaceflight.

Extracellular responses from single horizontal semicircular canal afferents in two rhesus monkeys were studied after recovery from a 14-day biosatellite (COSMOS 2044) orbital spaceflight. On the 1st postflight day, the mean gain for 9 different horizontal canal afferents, tested using one or several different passive yaw rotation waveforms, was nearly twice that for 20 horizontal canal afferents similarly tested during preflight and postflight control studies. Adaptation of the afferent response to passive yaw rotation on the 1st postflight day was also greater. These results suggest that at least one component of the vestibular end organ (the semicircular canals) is transiently modified after exposure to 14 days of microgravity. It is unclear whether the changes are secondary to other effects of microgravity, such as calcium loss, or an adaptive response. If the response is adaptive, then this report is the first evidence that the response of the vestibular end organ may be modified (presumably by the central nervous system via efferent connections) after prolonged unusual vestibular stimulation. If this is the case, the sites of plasticity of vestibular responses may not be exclusively within central nervous system vestibular structures, as previously believed.

Adaptation, Physiological

[A case of incessant junctional tachycardia in a female patient with aneurysm of the interauricular septum].

A permanent supraventricular tachycardia (SVT) was diagnosed in a 54-year-old hypertensive but cardiologically asymptomatic female patient, admitted to a surgery department for biliary lithiasis and hepatic echinococcosis. Heart rate was about 130 bpm and ECGs showed negative P waves in leads I, II, III, aVF, and precordial leads V2 to V6, being the RP' interval longer than P'R interval. Pharmacological intervention during Holter monitoring (20 hours) was instituted: following i.v. propranolol (4 mg), heart rate progressively decreased (to 112 bpm), mainly due to an increase in SVT RP' interval, and brief, spontaneous SVT interruptions occurred, preceded by P'R interval prolongation; SVT stopped after P' recording, and resumed after 2 sinus beats, (showing enlarged P waves and slightly prolonged PR interval), induced by cycle length shortening; later on, under i.v. amiodarone infusion (100 mg/hour) and coincident with the sleeping period, SVT cycle length progressively increased (to 600 msec), due to equivalent increases in P'R and R'P intervals. Two premature ventricular contractions (PVC) occurred during Holter monitoring at a coupling interval of 80-85% of SVT cycle length (480 msec): one PVC apparently originated in left ventricle lateral wall, captured the atria, which were activated 75 msec earlier than expected; the other PVC, apparently originated in left ventricle septoapical region, did not interfere with SVT cycle length. Before these data, a diagnosis of circus movement tachycardia, incorporating a concealed accessory pathway with slow retrograde conduction and ventricular insertion in the postoroseptal or left posterior paraseptal region, and showing minor impairment of antegrade AV nodal conduction, was made. Invasive electrophysiological study was then discarded. With combined oral antiarrhythmic therapy (amiodarone, 600 mg/d), plus propafenone, 450 mg/d), sinus rhythm was permanently restored, with evidence of intraatrial block, slightly prolonged PR interval and no preexcitation. Transesophageal echocardiography revealed a small atrial septal aneurysm associated with a small atrial septal defect; echocardiographic features were consistent with the hypothesis of incomplete regression of the atrial septal aneurysm after partial closure of the atrial septal defect. Abdominal surgery (cholecystectomy plus partial hepatic pericystectomy) was performed without any complications or SVT recurrences. During a 6-month follow-up period, maintaining amiodarone (200 mg/d) and propafenone (450 mg/d), the patient remained SVT-free, and Holter monitoring performed at 3 and 5 months showed permanent sinus rhythm and 1:1 AV conduction with slightly prolonged PR interval (less than 0.29 sec and shortening at faster heart rates). This case documents Holter monitoring capability for the evaluation of tachycardia mechanisms in patients with permanent SVT.

Amiodarone

Response properties of gerbil otolith afferents to small angle pitch and roll tilts.

The responses from isolated single otolith afferent fibers were obtained to small angle sinusoidal pitch and roll tilts in anesthetized gerbils. The stimulus directions that produced the maximum (response vector) and minimum response sensitivities were determined for each otolith afferent, with response vectors for the units being spread throughout the horizontal plane, similar to those reported for other species. A breadth of tuning measure was derived, with narrowly tuned neurons responding maximally to stimulation in one direction and minimally along an orthogonal ('null') direction. Most (approximately 80%) otolith afferents are narrowly tuned, however, some fibers were broadly tuned responding significantly to stimulations in any direction in the horizontal plane. The number of broadly tuned otolith afferents (approximately 20%) differs significantly from the more substantial number of broadly tuned vestibular nuclei neurons (88%) recently reported in rats.

Animals