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M J Correia

Publications and source records attributed to M J Correia.

At least 19 recordsLinked to original sources
PubMed2001

Effects of KCNQ channel blockers on K(+) currents in vestibular hair cells.

Linopirdine and XE991, selective blockers of K(+) channels belonging to the KCNQ family, were applied to hair cells isolated from gerbil vestibular system and to hair cells in slices of pigeon crista. In type II hair cells, both compounds inhibited a slowly activating, slowly inactivating component of the macroscopic current recruited at potentials above -60 mV. The dissociation constants for linopirdine and XE991 block were <5 microM. A similar component of the current was also blocked by 50 microM capsaicin in gerbil type II hair cells. All three drugs blocked a current component that showed steady-state inactivation and a biexponential inactivation with time constants of approximately 300 ms and 4 s. Linopirdine (10 microM) reduced inward currents through the low-voltage-activated K(+) current in type I hair cells, but concentrations up to 200 microM had little effect on steady-state outward K(+) current in these cells. These results suggest that KCNQ channels may be present in amniote vestibular hair cells.

Animals↗
PubMed2000

Effects of cationic substitutions on delayed rectifier current in type I vestibular hair cells.

The resting potassium current (I(KI)) in gerbil dissociated type I vestibular hair cells has been characterized under various ionic conditions in whole cell voltage-clamp. When all K(+) in the patch electrode solution was replaced with Na(+), (Na(+))(in) or Cs(+), (Cs(+))(in), large inward currents were evoked in response to voltage steps between -90 and -50 mV. Activation of these currents could be described by a Hodgkin-Huxley-type kinetic scheme, the order of best fit increasing with depolarization. Above approximately -40 mV currents became outward and inactivated with a monoexponential time course. Membrane resistance was inversely correlated with external K(+) concentration. With (Na(+))(in), currents were eliminated when K(+) was removed from the external solution or following extracellular perfusion of 4-aminopyridine, indicating that currents flowed through I(KI) channels. Also, reduction of K(+) entry through manipulation of membrane potential reduced the magnitude of the outward current. Under symmetrical Cs(+), 0 K(+) conditions I(KI) is highly permeable to Cs(+). However, inward currents were reduced when small amounts of external K(+) were added. Higher concentrations of K(+) resulted in larger currents indicating an anomalous mole fraction effect in mixtures of external Cs(+) and K(+).

4-Aminopyridine↗
PubMed2000

Hair cell and supporting cell density and distribution in the normal and regenerating posterior crista ampullaris of the pigeon.

The numbers of supporting cells and the numbers and types of hair cells in three distinct longitudinal regions through the posterior canal cristae of control and streptomycin-treated pigeons were determined using stereological techniques. For control cristae, type I (3758) and type II (3517) hair cells occurred in approximately equal numbers. However, the proportions varied in different longitudinal zones: Zone I (peripheral region) had four times more type II hair cells (2083) than type I (483), while Zone II (intermediate region) had almost seven times more type I (2517) than type II (367) hair cells and Zone III (central region) had relatively equal numbers of type I (758) and type II (1067) hair cells. Novel findings included the following: (1) immediately after the post-injection sequence (PIS) of streptomycin, there was a significant reduction in both hair cells (-93%) and supporting cells (-45%); (2) by 70 days after the PIS, the population of type I hair cells returned to control values (however, the normal complement of complex calyces took 1 year to recover); (3) during the first 143 days after the PIS, the number of type I and type II hair cells across all zones returned linearly with about the same slope (46 and 43 cells per day, respectively), although the rate of return differed significantly in different zones; (4) there was a massive overproduction of hair cells (+150%) and supporting cells (+120%) during the first 5 months of recovery; and (5) during the first year after the PIS, both hair cells and supporting cells increased and their increases in numbers were correlated (r = 0.88, P < 0.01). Knowledge of the sequence and numbers of regenerating hair cells may help elucidate common modes of cell survival, recovery, and compensation from neural insult.

Animals↗
PubMed2000

Multiple endocrine neoplasia type 2A. Study of a family.

INTRODUCTION: Pheochromocytomas (Pheo) can occur sporadically, isolated or in association with other neuroendocrine lesions. In multiple endocrine neoplasia type 2A (MEN-2A), Pheo is associated to medullary thyroid carcinoma (MTC) or its precursor, C-cell hyperplasia (CCH) and parathyroid hyperplasia. Genetic screening provides early diagnosis and preventive treatment. In order to validate DNA analysis as a reliable method of early identification of gene carriers, we compared the results of genetic screening with clinical, biochemical, imaging and pathological findings in the members of an affected family. POPULATION AND METHODS: The diagnosis of a bilateral necrotic Pheo in a female patient led to the study of a family with four generations, aged 3 to 78 years (mean = 30.3 yrs). The study included a clinical examination; basal and pentagastrin stimulated calcitonin values; urinary catecholamines and their metabolites; serum calcium and a genetic study (direct sequence of PCR products from genomic DNA isolated from leucocytes using specific primers in exon 11 of the RET protooncogene of chromosome 10). The radiologic study, gammagraphic study (131I-MIBG) and magnetic resonance study were performed in members with clinical suspicion of Pheo. RESULTS: Seven out of nine patients had a mutation on codon 634 of exon 11 of RET (TGC-CGC), leading to cysteine arginine substitution in the codified protein; all gene carriers had biochemical markers of MTC/CCH and four of Pheo. The Pheo patients underwent adrenalectomy (bilateral in three) and all the gene carriers underwent prophylactic thyroidectomy. The pathologic findings were: MTC in four (metastasized in one); CCH in three and parathyroid hyperplasia in one. CONCLUSIONS: Phenotypic penetration of RET mutation was 100% for MTC/CCH, but only 57% of the gene carriers had Pheo. Genetic screening allowed early prophylactic treatment in four out of seven patients; pathologic findings revealed several evolutionary stages of the disease. Patients not yet showing Pheo are under close clinical and laboratory surveillance.

Adolescent↗
PubMed2000

Extra-adrenal pheochromocytoma (paraganglioma).

The authors describe the case of a 19-year-old female patient with an abdominal paraaortic extra-adrenal pheochromocytoma (paraganglioma), presenting arterial hypertension. The predominant catecholamine produced by the tumor was norepinephrine (4110 pg/ml; normal < 450 pg/ml). 131I metaiodobenzylguanidine (131I-MIBG), computed tomography and magnetic resonance imaging allowed location and characterization of the tumor. Histologically the tumor (weight = 34.2 g; 5.8 x 4 x 3 cm) was a typical pheochromocytoma.

Abdominal Neoplasms↗
PubMed1999

Artifactual voltage response recorded from hair cells with patch-clamp amplifiers.

Patch-clamp amplifiers (PCAs) are commonly used to characterize voltage- and current-clamp responses in the same cell. However, the cell membrane voltage response can be severely distorted by PCAs working in the current-clamp mode. Here we compare the voltage response of pigeon semicircular canal hair cells in situ, recorded with two different PCAs, and with a classic microelectrode bridge amplifier (BA). We found that the voltage response of hair cells recorded with PCAs differed significantly from that recorded with the BA. The true hair cell membrane voltage response to positive current steps was characterized by a strongly damped oscillation, whose frequency and duration depended on hair cell location in the sensory crista ampullaris.

Animals↗
PubMed1999

Electrical response properties of avian lagena type II hair cells: a model system for vestibular filtering.

Data presented represent the first electrical recordings from avian lagena type II hair cells. The perforated-patch variant of the whole cell recording technique was used to investigate how the macroscopic currents shaped the voltage response of the hair cells. Voltage-clamp data separated cells into two broad classes on the basis of differences in activation rates, rates and degree of inactivation, and pharmacological sensitivity. Current-clamp recordings revealed low-quality membrane voltage oscillations (Qc < 1) during pulse current injections. Oscillation frequency correlated with activation rate of the macroscopic currents. The quality of membrane oscillations (Qc) varied linearly with frequency for cells with little inactivation. For cells with rapid inactivation, no relationship was found between Qc and frequency. Rapid inactivation may serve to extend the bandwidth of vestibular hair cells. The frequency measured from voltage responses to pulsed currents may reflect the corner frequency of the cell. The filtering properties of avian lagena hair cells are like those found in all other vestibular end organs, suggesting that the electrical membrane properties of these cells are not responsible for specializing them to a particular stimulus modality.

4-Aminopyridine↗
PubMed1999

Regional distribution of ionic currents and membrane voltage responses of type II hair cells in the vestibular neuroepithelium.

Basolateral ionic currents and membrane voltage responses were studied in pigeon vestibular type II hair cells using a thin slice through either the semicircular canal (SCC) crista or utricular macular epithelium. Whole cell tight-seal patch-clamp recording techniques were used. Current-clamp and voltage-clamp studies were carried out on the same cell. One hundred ten cells were studied in the peripheral (Zone I) and central (Zone III) zones of the SCC crista, and 162 cells were studied in the striolar (S Zone) and extrastriolar (ES Zone) zones of the utricular macula. One of the major findings of this paper is that hair cells with fast activation kinetics of their outward currents are found primarily in one region of the SCC crista and utricular macula, whereas hair cells with slow activation kinetics are found in a different region. In Zone I of the crista, 95% of the cells have fast activation kinetics ("fast" cells) and in Zone III of the crista, 86% of the cells have slow activation kinetics ("slow" cells). In the utricular macula slice, 100% of the cells from the S Zone are slow cells, whereas 86% of the cells from the ES Zones are fast cells. Oscillation frequency (f) and quality factor (Q) of the damped oscillations of the membrane potential during extrinsic current injections were studied in hair cells in the different regions. The slow cells in Zone III and in the S Zone have a statistically significantly lower f, as a function of the amplitude of injected current, when compared with the fast cells in Zone I and the ES Zone. Although Q varied over a small range and was <2.6 for all cells tested, there was a statistically significant difference between Q for the membrane oscillations of the slow cells and fast cells in response to a range of current injections.

Animals↗
PubMed1999

[The variability of the heart rate in the first 24 hours after fibrinolytic therapy in acute myocardial infarct].

AIM OF THE STUDY: The role of heart rate variability changes in the appraisal of reperfusion after fibrinolytic therapy in acute myocardial infarction is still controversial. The aim of this study was to analyze the influence of reperfusion and infarct site on heart rate variability within 24 hours after infarction. PATIENTS AND METHODS: We studied 45 patients with a mean age = 56.3 +/- 12.4 years, 25 with anterior infarction and 20 with inferior infarction. The reperfusion was defined by the simultaneous presence of three classic noninvasive criteria (fast relief of pain, fast regression of ST segment elevation and early peak of CK). We studied heart rate variability parameters in time-domain and frequency-domain on a 24-hour Holter ECG started at the same time as fibrinolytic therapy. RESULTS: Thirty-three patients showed reperfusion. We did not find significant differences in the several parameters of heart rate variability between patients with reperfusion and patients without reperfusion, but the patients with anterior wall infarction showed a significant reduction in SDNN in comparison with patients with inferior wall infarction (84 +/- 28 ms vs 102 +/- 30 ms; p = 0.05). pNN50 (5.3 +/- 7.2 ms vs 10.5 +/- 9.8 ms; p = 0.04), LF (618 +/- 591 ms2 vs 1374 +/- 1761 ms2; p = 0.05) and TP (1415 +/- 1199 ms2/Hz vs 3015 +/- 4243 ms2/Hz). CONCLUSION: These data suggest a relationship between infarct severity and sympathetic activation and/or reduction of vagal modulation, but a potential beneficial effect of reperfusion on autonomic nervous system alterations was not evident in the first day of acute myocardial infarction.

Adult↗
PubMed1998

Neuronal plasticity: adaptation and readaptation to the environment of space.

While there have been few documented permanent neurological changes resulting from space travel, there is a growing literature which suggests that neural plasticity sometimes occurs within peripheral and central vestibular pathways during and following spaceflight. This plasticity probably has adaptive value within the context of the space environment, but it can be maladaptive upon return to the terrestrial environment. Fortunately, the maladaptive responses resulting from neuronal plasticity diminish following return to earth. However, the literature suggests that the longer the space travel, the more difficult the readaptation. With the possibility of extended space voyages and extended stays on board the international space station, it seems worthwhile to review examples of plastic vestibular responses and changes in the underlying neural substrates. Studies and facilities needed for space station investigation of plastic changes in the neural substrates are suggested.

Adaptation, Physiological↗
PubMed1998

Recovery of semicircular canal primary afferent activity in the pigeon after streptomycin ototoxicity.

Recovery of semicircular canal primary afferent activity in the pigeon after streptomycin ototoxicity. J. Neurophysiol. 80: 3297-3311, 1998. The electrophysiological activity of horizontal semicircular canal primary afferents (HSCPA) was investigated in vivo in the barbiturate-anesthetized pigeon by means of extracellular single-fiber vestibular nerve action potential recordings. The spontaneous and driven discharges to pulse (step/trapezoid waveform, peak velocity = 120 degrees/s) and sum-of-sines (0.03, 0.09, 0.21, 0.39, 0.93, 1.83 Hz, peak velocity = 30 degrees/s for each frequency) rotations were measured both in normal control animals and a group of animals at 30, 40, 50, 60, 71, and 150 days postinjection sequence (PIS) of streptomycin sulfate. Prior to 30 days PIS, the activity in the nerve was not appropriately modulated during and after rotation. At 30 days PIS and thereafter, the responses resembled those observed in control animals but with systematic changes in parameters of fitted pulse responses and fitted Bode plots as days PIS increased. The return of parameters characterizing the neural dynamics of the semicircular canals were monotonic and could be best described by either linear or exponential functions. After 30 days PIS, the mechanical cupula-endolymph system, the function of which can be inferred from the cupula long time constant (tauL) following step velocity, did not change systematically (tauL = 6.92 +/- 3.96, 8.64 +/- 5.52, 8.35 +/- 4.21, 10.00 +/- 2.79, 9.05 +/- 3.67, 7.05 +/- 2.72; means +/- SD). However, the mean gain (G) of the HSCPA response to pulse rotation nearly doubled between 30 and 150 days PIS (from 1.31 +/- 0. 39 to 2.40 +/- 1.04) and returned linearly to control values (G = 2. 39 +/- 0.77) over this time period [G = 1.33 + 0.009(PIS-30), R2 = 0. 92, P < 0.05]. Meanwhile, neural adaptation as quantitated using a fractional operator, k, decayed exponentially (single exponential) to an asymptote. The time constant of this exponential was approximately 55 days [k = 0.034 + 0.33e-(PIS-30)/55.4, R2 = 0.99, P < 0.01]. Features of the spontaneous discharge previously shown to be correlated with k changed appropriately. That is, the coefficient of variation (CV) and frequency of firing (FF) decayed and grew asymptotically, respectively. These parameters also exhibited an exponential time course of return to control values from 30 to 150 days PIS [CV = 0.44 + 0.65e-(PIS-30)/21.5, R2 = 0.96, P < 0.01, and FF = 39.97 + 101.42(1 - e-(PIS-30)/32.6), R2 = 0.97, P < 0.01]. The trends of recovery for G, k, and tauL derived from analysis of the pulse response were confirmed by strong positive correlations with best fitted parameters obtained from analysis of the sum-of-sines frequency domain response of HSCPAs. There were statistically significant correlations (r = 0.90, P < 0.05 and r = 0.93, P < 0.05) between parameters (G, k) derived from pulse responses and those (G', k') from sum-of-sines responses, respectively. The cupula time constant based on sum-of-sines' data (tau'L) showed no statistically significant change between 30 and 150 days PIS (P > 0.05, analysis of variance). Thus the results in present study indicate that both the spontaneous discharge and the driven response to rotation of pigeon HSCPAs recovered their normal physiological status between 30 and 150 days PIS after hair cell death due to aminoglycoside ototoxicity. The recovery was systematic for the parameters chosen to be tested with the exception of the cupula long time constant, tauL. The mechanisms (changes in ciliary dynamics, changes in hair cell ionic currents, changes in bouton terminals, etc.) underlying these changes await further morphophysiological studies.

Action Potentials↗
PubMed1997

Ionic currents in regenerating avian vestibular hair cells.

By applying the conventional whole-cell patch-clamp technique in combination with the slice procedure, we have investigated the properties of avian semicircular canal hair cells in situ. Passive and active electrical properties of hair cells from control animals have been compared with those of regenerating hair cells following streptomycin treatment (that killed almost all hair cells). Regenerating type II hair cells showed patterns of responses qualitatively similar to those of normal hair cells. However, parameters reflecting the total number of ionic channels and the surface area of type II hair cells changed during recovery-suggesting that new hair cells came from smaller precursors which (with time) reacquired the same electrophysiological properties as normal hair cells. Finally, we have investigated the ionic properties of a small sample of type 1 hair cells. Ionic currents of regenerating type I hair cells did not show, at least in the temporal window considered (up to 10 weeks from the end of the streptomycin treatment), the typical ionic currents of normal type I hair cells, but expressed instead ionic currents resembling those of type II hair cells. The possibility that regenerating type I hair cells can transdifferentiate from type II hair cells is therefore suggested.

Animals↗
PubMed1997

Evidence for an Na(+)-K(+)-Cl- cotransporter in mammalian type I vestibular hair cells.

In amniotes, there are two types of hair cells, designated I and II, that differ in their morphology, innervation pattern, and ionic membrane properties. Type I cells are unique among hair cells in that their basolateral surfaces are almost completely enclosed by an afferent calyceal nerve terminal. Recently, several lines of evidence have ascribed a motile function to type I hair cells. To investigate this, elevated external K+, which had been used previously to induce hair cell shortening, was used to induce shape changes in dissociated mammalian type I vestibular hair cells. Morphologically identified type I cells shortened and widened when the external K+ concentration was raised isotonically from 2 to 125 mM. The shortening did not require external Ca2+ but was abolished when external Cl- was replaced with gluconate or sulfate and when external Na+ was replaced with N-methyl-D-glucamine. Bumetanide (10-100 microM), a specific blocker of the Na(+)-K(+)-Cl- cotransporter, significantly reduced K(+)-induced shortening. Hyposmotic solution resulted in type I cell shape changes similar to those seen with high K+, i.e., shortening and widening. Type I cells became more spherical in hyposmotic solution, presumably as a result of a volume increase due to water influx. In hypertonic solution, cells became narrower and increased in length. These results suggest that shape changes in type I hair cells induced by high K+ are due, at least in part, to ion and solute entry via an Na(+)-K(+)-Cl- cotransporter, which results in cell swelling. A scheme is proposed whereby the type I hair cell depolarizes and K+ leaves the cell via voltage-dependent K+ channels and accumulates in the synaptic space between the type I hair cell and calyx. Excess K+ could then be removed from the intercellular space by uptake via the cotransporter.

Animals↗
PubMed1997

Electrophysiological properties of vestibular sensory and supporting cells in the labyrinth slice before and during regeneration.

The whole cell patch-clamp technique in combination with the slice preparation was used to investigate the electrophysiological properties of pigeon semicircular canal sensory and supporting cells. These properties were also characterized in regenerating neuroepithelia of pigeons preinjected with streptomycin to kill the hair cells. Type II hair cells from each of the three semicircular canals showed similar, topographically related patterns of passive and active membrane properties. Hair cells located in the peripheral regions (zone I, near the planum semilunatum) had less negative resting potentials [0-current voltage in current-clamp mode (Vz) = -62.8 +/- 8.7 mV, mean +/- SD; n = 13] and smaller membrane capacitances (Cm = 5.0 +/- 0.9 pF, n = 14) than cells of the intermediate (zone II; Vz = -79.3 +/- 7.5 mV, n = 3; Cm = 5.9 +/- 1.2 pF, n = 4) and central (zone III; Vz = -68.0 +/- 9.6 mV, n = 17; Cm = 7.1 +/- 1.5 pF, n = 18) regions. In peripheral hair cells, ionic currents were dominated by a rapidly activating/inactivating outward K+ current, presumably an A-type K+ current (IKA). Little or no inwardly rectifying current was present in these cells. Conversely, ionic currents of central hair cells were dominated by a slowly activating/inactivating outward K+ current resembling a delayed rectifier K+ current (IKD). Moreover, an inward rectifying current at voltages negative to -80 mV was present in all central cells. This current was composed of two components: a slowly activating, noninactivating component (Ih), described in photoreceptors and saccular hair cells, and a faster-activating, partially inactivating component (IK1) also described in saccular hair cells in some species. Ih and IK1 were sometimes independently expressed by hair cells. Hair cells located in the intermediate region (zone II) had ionic currents more similar to those of central hair cells than peripheral hair cells. Outward currents in intermediate hair cells activated only slightly more quickly than those of the cells of the central region, but much more slowly than those of the peripheral cells. Additionally, intermediate hair cells, like central hair cells, always expressed an inward rectifying current. The regional distribution of outward rectifying potassium conductances resulted in macroscopic currents differing in peak-to-steady state ratio. We quantified this by measuring the peak (Gp) and steady-state (Gs) slope conductance in the linear region of the current-voltage relationship (-40 to 0 mV) for the hair cells located in the different zones. Gp/Gs average values (4.1 +/- 2.1, n = 15) from currents in peripheral hair cells were higher than those from intermediate hair cells (2.3 +/- 0.8, n = 4) and central hair cells(1.9 +/- 0.8, n = 21). The statistically significant differences (P < 0.001) in Gp/Gs ratios could be accounted for by KA channels being preferentially expressed in peripheral hair cells. Hair cell electrophysiological properties in animals pretreated with streptomycin were investigated at approximately 3 wk and approximately 9-10 wk post injection sequence (PIS). At 3 wk PIS, hair cells (all zones combined) had a statistically significantly (P < 0.001) lower Cm (4.6 +/- 1.1 pF, n = 24) and a statistically significantly (P < 0.01) lower Gp(48.4 +/- 20.8 nS, n = 26) than control animals (Cm = 6.2 +/- 1.6 pF, n = 36; Gp = 66 +/- 38.9 nS, n = 40). Regional differences in values of Vz, as well as the distribution of outward and inward rectifying currents, seen in control animals, were still obvious. But, differences in the relative contribution of the expression of the different ionic current components changed. This result could be explained by a relative decrease in IKA compared with IKD during that interval of regeneration, which was particularly evident in peripheral hair cells. (ABSTRACT TRUNCATED)

Animals↗
PubMed1997

Vertical optokinetic nystagmus and after-responses during backward tilt.

METHOD: Vertical optokinetic nystagmus (VOKN) and after-responses were detected in nine subjects using the corneo-retinal potential (CRP) technique and an infrared video camera detection apparatus (ISCAN) simultaneously. The ISCAN method produced a much smaller inter-subject variability, a higher linear regression coefficient (0.94) when vertical eye position was regressed against vertical target position (+/- 30 degrees, 5 degrees increments). Detected by ISCAN, VOKN responses were measured at 3 angles of pitch head (and body) tilt: upright (0 degrees), supine (90 degrees), and declined 45 degrees below horizontal (135 degrees). Two stripe velocities (40 degrees.s-1 and 60 degrees.s-1) were used. RESULTS: In six of the nine subjects (67%) and in 40/54 conditions (74%) for all subjects, upward (slow phase velocity up) VOKN gain was greater than downward VOKN gain for both stripe velocities at all tilt angles. The gain for both upward and downward VOKN decreased as stripe velocity increased from 40-60 degrees.s-1, which suggests that both upward and downward VOKN systems were starting to saturate. Across subjects, a mean up-down asymmetry index, I, increased monotonically as the subjects declined. The slope of the monotonic function was greater for 60 degrees.s-1 stripe velocity than for 40 degrees.s-1 stripe velocity. The mean of all subjects' individual asymmetry ratios (ASYM) also increased as tilt increased but the slope of the best fitted regression line was not statistically significantly different from zero (p > 0.05). CONCLUSION: Optokinetic after-responses observed in the present study were of two types: 1) resetting of the eye by a drift, with nystagmus superimposed, from a beating field (eye position) that occurred during optokinetic stimulation; and 2) resetting of the eye without nystagmus superimposed. Upward VOKN produced the greatest number of after-responses. The beating field of VOKN was not correlated with pitch tilt.

Adult↗