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Biomedical subjects

A Ferroni

Publications and source records attributed to A Ferroni.

At least 55 records · Page 3Linked to original sources
PubMed1989

Cross-talk between receptors coupled to calcium currents in adult but not neonatal rat sensory neurons.

In adult rat sensory neurons Ca2+ currents were studied with the whole-cell patch-clamp technique. Two categories of neuromodulators, known to activate different 2nd messenger systems: 1) angiotensin II (AII), bovine serum albumin (BSA), Acetylcholine (ACh) and 2) GABA, stimulated the low-voltage activated (LVA) and inhibited the high voltage activated (HVA) currents, respectively. The simultaneous application of the two types of drugs failed to inhibit the HVA current via a putative cross-talk between the two 2nd messengers.

Aging↗
PubMed1988

The relation between supraventricular tachyarrhythmias and left ventricular dysfunction after acute myocardial infarction.

The clinical characteristics of supraventricular tachyarrhythmias (SVTA) and their relation to left ventricular dysfunction were assessed in 208 consecutive patients with recent myocardial infarction. Arrhythmias were quantified on hospital discharge by 24 hour electrocardiographic recording. All the variables were evaluated between the second and the fourth week after infarction. SVTA occurred in 113 (54%) patients: Supraventricular premature beats (SVPB) in 49 (24%), frequent or repetitive SVPB in 37 (18%), atrial or junctional tachycardia in 23 (11%), atrial flutter or fibrillation in 4 (2%). Most of these arrhythmias occurred in the absence of symptoms, and the most complex forms were always selflimiting. No relation was found among the presence of different forms of SVTA and sex, coronary risk factors, previous history of ischemic heart disease, type or site of acute myocardial infarction, NYHA functional class. Age, left atrial dimension (LAD), cardio-thoracic ratio (CTR) and left ventricular ejection fraction (LVEF) at rest differed significantly among three groups of patients: those without SVTA, those with SVPB less than 100 per hour and those with frequent-repetitive SVPB or atrial-junctional tachycardia. The more SVTA complexity, the worse LAD, CTR, LVEF and the higher the age. Multivariate discriminant analysis showed that CTR was directly and LVEF inversely related to the occurrence of SVPB less than 100 per hour, while the presence of frequent-repetitive SVPB or supraventricular tachycardia was closely related to increasing age, LAD, CTR and decreasing LVEF. Patients with atrial fibrillation always showed the worst values of LAD, CTR, LVEF and age. The results of the present study show that different types of SVTA occurring at discharge from hospital after myocardial infarction are clinically benign, but always suggestive of different degrees of left ventricular dysfunction.

Adult↗
PubMed1987

Three types of ion channels are present on the plasma membrane of Friend erythroleukemia cells.

In Friend murine erythroleukemia cells the presence of ion channels was investigated with the patch-clamp technique. During the first 48 hours after cell seeding, three types of ion channels, with the following order of membrane density, were found: i) a Ca2+-dependent K+ channel, fully activated at a cytosolic Ca2+ concentration of 10(-6) M and moderately activated at 10(-7)M; ii) a monovalent cation channel non voltage-activated, with an open-close kinetics dependent on the pressure gradient across the patch; iii) a chloride channel with a slow open-close kinetics. The latter two channels were labile and did not survive during intracellular perfusion. The membrane potential of the leukemia cells was not constant, but underwent large (tens of millivolts) fluctuations due to the opening of a few channels. The average resting membrane potential recorded in this study agrees with that measured in these cells by means of the accumulation ratio of the lipophilic cation Tetraphenylphosphonium.

Animals↗
PubMed1987

Activation of a muscarinic receptor selectively inhibits a rapidly inactivated Ca2+ current in rat sympathetic neurons.

Sympathetic neurons dissociated from the superior cervical ganglion of 2-day-old rats were studied by whole-cell patch clamp and by fura-2 measurements of the cytosolic free Ca2+ concentration, [Ca2+]i. Step depolarizations in the presence of tetrodotoxin and hexamethonium triggered two Ca2+ currents that differed in the voltage dependence of activation and kinetics of inactivation. These currents resemble the L and N currents previously described in chicken sensory neurons [Nowycky, M. C., Fox, A. P. & Tsien, R. W. (1985) Nature (London) 316, 440-442]. Treatment with acetylcholine resulted in the rapid (within seconds), selective, and reversible inhibition of the rapidly inactivated, N-type current, whereas the long-lasting L-type current remained unaffected. The high sensitivity to blocker drugs (atropine, pirenzepine) indicated that this effect of acetylcholine was due to a muscarinic M1 receptor. Intracellular perfusion with nonhydrolyzable guanine nucleotide analogs or pretreatment of the neurons with pertussis toxin had profound effects on the Ca2+ current modulation. Guanosine 5'-[gamma-thio]triphosphate caused the disappearance of the N-type current (an effect akin to that of acetylcholine, but irreversible), whereas guanosine 5'-[beta-thio]diphosphate and pertussis toxin pretreatment prevented the acetylcholine-induced inhibition. In contrast, cAMP, applied intracellularly together with 3-isobutyl-1-methylxanthine, as well as activators and inhibitors of protein kinase C, were without effect. Acetylcholine caused shortening of action potentials in neurons treated with tetraethylammonium to partially block K+ channels. Moreover, when applied to neurons loaded with the fluorescent indicator fura-2, acetylcholine failed to appreciably modify [Ca2+]i at rest but caused a partial blunting of the initial [Ca2+]i peak induced by depolarization with high K+. This effect was blocked by muscarinic antagonists and pertussis toxin and was unaffected by protein kinase activators. Thus, muscarinic modulation of the N-type Ca2+ channels appears to be mediated by a pertussis toxin-sensitive guanine nucleotide-binding protein and independent of both cAMP-dependent protein kinase and protein kinase C.

Acetylcholine↗
PubMed1987

[Efficacy of propafenone in the treatment of ventricular hyperkinetic arrhythmias in subjects with a history of myocardial infarction].

A placebo-controlled single-blind study was performed to evaluate the efficacy of oral propafenone on stable potentially malignant ventricular tachyarrhythmias in 13 patients who had suffered a myocardial infarction two months or longer before the trial. All patients exhibited at a 24 hour Holter monitoring a minimum mean frequency of 10 ventricular premature depolarizations (VPDs) per hour and repetitive VPDs. Ventricular tachyarrhythmias characterization was obtained by means of multiple Holter monitorings and exercise stress testings. Propafenone was considered as effective when a well-defined quantitative and qualitative reduction of ventricular tachyarrhythmias was reached. After an initial placebo phase, patients received propafenone 450 mg or 900 mg daily. Acute effectiveness of propafenone was proved in 8 on 13 patients (62%) who showed a significative reduction of VPDs (89%, p less than 0.02) and a suppression of the most complex forms of ventricular tachyarrhythmic events. The efficacy of propafenone was confirmed, three months later, in each patient, side effects were infrequent, minimal and of no clinical consequence. Oral propafenone can be considered as an effective drug for reducing the level of potentially malignant ventricular tachyarrhythmias in patients with previous myocardial infarction.

Aged↗
PubMed1986

alpha Latrotoxin of the black widow spider venom opens a small, non-closing cation channel.

alpha Latrotoxin, a presynaptically acting polypeptide neurotoxin, induces massive neurotransmitter release from both synapses of vertebrates and the neurosecretory cells of the line PC12, derived from a rat pheochromocytoma. Single PC12 cells, differentiated by treatment with nerve growth factor, were used to investigate by the patch-clamp technique i) the alterations of the resting cell conditions (membrane potential and resistance) and ii) the microscopic mechanism of the permeability changes that underly the response to alpha LTx. The toxin was found to open a channel, 15 pS in conductance, that is permeable to various cations (Na+, K+ and probably Ca2+) and has little tendency to close. This channel is different from the classical voltage- and receptor-operated channels present in PC12 cells, as well as from the large conductances induced by the toxin in artificial lipid membranes.

Animals↗
PubMed1986

Exercise radionuclide ventriculography after uncomplicated myocardial infarction: what could we gain from the analysis of LVEF throughout the whole test?

To assess the usefulness of a step by step evaluation of exercise left ventricular ejection fraction (LVEF), 219 consecutive patients with recent uncomplicated myocardial infarction and 30 normal subjects underwent a symptom-limited cycloergometer test followed by exercise radionuclide ventriculography (ExRNV). LVEF was monitored throughout the whole test. 49 patients underwent coronary arteriography for clinical reasons. 5 patterns of exercise LVEF could be observed: progressive increase: 55 patients (25%) and 27 normal subjects (90%); progressive decrease: 37 patients (17%); initial increase followed by significant decrease: 54 patients (25%); lack of initial modification and terminal decrease: 35 patients (16%); no modification: 38 patients (17%) and 3 normal subjects (10%). Grouping the patients in this fashion allowed us to increase the specificity of ExRNV from 70% to 100%, without loss of sensitivity (95%). As for the patients in subgroup C, 32/54 showed unequivocal ECG ischaemic changes, occurring simultaneously with LVEF decrease; in 33/54 LVEF dropped during the last workload; in 25/54 the last stage LVEF was equal to or higher than the basal LVEF. The statistical analysis showed that ischaemic ECG changes (P less than 0.0001), exercise-induced wall-motion abnormalities (P less than 0.0001), and the presence of multivessel coronary artery disease (P less than 0.0001) were significantly more frequent in patients showing patterns (b)-(d), which should be considered as ischaemic. Our method allowed the unequivocal identification of ischaemic patterns in LVEF during exercise, which might be missed if only its basal and final values are considered.

Adult↗
PubMed1986

Clinical significance of supraventricular tachyarrhythmias after acute myocardial infarction.

160 survivors of acute myocardial infarction (AMI) were evaluated to assess the clinical significance of supraventricular tachyarrhythmias (SVTA) occurring at discharge from the hospital after the acute event. All the variables considered for the study were estimated before hospital discharge; arrhythmias were quantified with a 24 h Holter ECG monitoring system. SVTA occurred in 88 patients (55%). Single or repetitive supraventricular premature beats were found in 65 (41%), paroxysmal atrial or junctional tachycardias in 20 (12%), bouts of atrial flutter or fibrillation in 3 (2%). Bivariate statistical analysis showed no relationship between sex, previous cardiovascular history, type, and location of AMI and SVTA occurrence. A close positive relationship was found between age, left atrial dimension (LAD), cardio-thoracic ratio (CTR) and SVTA occurrence; an inverse relationship was found for left ventricular ejection fraction (LVEF). The presence of SVTA appeared significantly related to age above 55 years, to LAD greater than 40 mm, to LVEF less than 45%, to serum creatine kinase peak levels over 1400 U l-1 and to CTR over 0.49. Multivariate statistical analysis showed that five variables are important in discriminating patients suffering from SVTA: age, LAD, LVEF, left ventricular fractional shortening, and CTR. SVTA occurring at discharge from hospital after AMI are indicative of impaired left ventricular pump function.

Analysis of Variance↗
PubMed1986

Properties of the hyperpolarizing-activated current (if) in cells isolated from the rabbit sino-atrial node.

Individual cells were isolated from the sino-atrial node area of the rabbit heart using an enzyme medium containing collagenase and elastase. After enzymatic treatment the cells were placed in normal Tyrode solution, where beating resumed in a fraction of them. Isolated cells were studied in the whole cell configuration. Action potentials as well as membrane currents under voltage-clamp conditions were similar to those in multicellular preparations. Pulses to voltages more negative than about -50 mV caused activation of the hyperpolarizing-activated current, if. Investigation of the properties of this current was carried out under conditions that limited the influence of other current systems during voltage clamp. The if current activation range usually extended approximately from -50 to -100 mV, but varied from cell to cell. In several cases, pulsing to the region of -40 mV elicited a sizeable if. Both current activation and deactivation during voltage steps had S-shaped time courses. A high variability was however observed in the sigmoidal behaviour of if kinetics. Plots of the fully-activated current-voltage (I-V) relation in different extracellular Na and K concentrations showed that both ions carry the current if. While changes in the external Na concentration caused the current I-V relation to undergo simple shifts along the voltage axis, changes in extracellular K concentration were also associated with changes in its slope. Again, a large variability was observed in the increase of I-V slope on raising the external K concentration. The current if was strongly depressed by Cs, and the block induced by 5 mM-Cs was markedly voltage dependent. Adrenaline (1-5 microM) and noradrenaline (1 microM) increased the current if around the half-activation voltage range and accelerated its activation at more negative voltages. Often, however, drug application failed to elicit any modification of if. Current run-down was observed in nearly all cells, although at a highly variable rate. It was accelerated by raising the extracellular K concentration but did not show a marked use dependence. Both the if activation curve and the fully activated I-V relation were affected by run-down, the former being shifted to more negative values along the voltage axis and the latter being depressed with no apparent change of the if reversal potential.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗
PubMed1985

Cadmium-induced blockade of the cardiac fast Na channels in calf Purkinje fibres.

The fast transient inward current elicited by depolarizations above about -60 mV in calf Purkinje fibres was found to be depressed by Cd in concentrations less than 1 mM. The Cd-sensitive current, which strongly depended on external Na, was recorded in the presence of 2 mM MnCl2 and was blocked by TTX, indicating that a contamination from slow Ca-dependent currents could be discounted. The current reduction caused by Cd was also observed in nominally Ca-free solutions. The Cd-induced depression of the fast Na current was not accompanied by changes in the current kinetic parameters, as revealed by comparing inactivation curves and peak current voltage relations at different Cd concentrations, and could be attributed to a voltage-independent channel blocking action. Half-blockade occurred at 0.182 +/- 0.06 mM (n = 4). Plots of peak current amplitude as a function of the Cd concentration showed that the cooperation of two Cd ions was required to block a single channel.

Animals↗
PubMed1985

A voltage-dependent K+ channel controlling the membrane potential in frog oocytes.

Full-grown frog ovarian oocytes (Rana esculenta), were voltage clamped with a conventional two-microelectrode system. Depolarizations from a holding potential of--60 mV produced slowly developing outward currents. Two-step clamp experiments showed that, in Ringer's solution, this current has a reversal potential at about--84 mV. Substitution of either sodium or chloride with impermeant ions in the external solution did not alter significantly the activation of the current nor its reversal potential. Increasing the potassium ions concentration caused a shift on the reversal potential in the positive direction with a slope of about 48 mV per decade. The presence of TEA ions (50 mM) in the external solution partially reduced the current. It is concluded that the membrane of full-grown frog ovarian oocytes possesses voltage-dependent ionic channels permeated mainly by potassium. They appear to play an important role in the control of membrane potential.

Animals↗
PubMed1985

[Ion channels in cardiac tissue. Validity and limits of cellular electrophysiology in the interpretation of clinical data].

New experimental methods in cellular electrophysiology allowed the identification and characterization of specific "ion channels" in the plasma membrane of cardiac cells in different regions of the heart. Function and implication of the "ion channels" have been considered in 1) the initiation of the heart-beat, 2) the chronotropic and inotropic effects of neurotransmitters (nor-epinephrine-acetylcholine), 3) the action mechanism of the steroid cardioactive drugs, 4) the cardiac repolarization, 5) the physiopathology of several arrhythmias. Moreover clinical data useful for the indirect evaluation of the ion channels function have been pointed out, stressing the ion channels models contribution for the cardiac pathology interpretation, particularly in the cardiac arrhythmias field.

Acetylcholine↗
PubMed1984

Barium-induced blockade of the inward rectifier in calf Purkinje fibres.

The Ba-induced blockade of iK1 in calf Purkinje fibres was studied in the low concentration range (3-1,000 microM). The results showed that the blockade induced by hyperpolarizations was time-dependent, and that the rate of blockade increased with the Ba concentration and the negative pulse amplitude. At Ba concentrations higher than 1 mM the time course of iK1 blockade was not separable from the capacity transient. At these concentrations, and in a limited voltage range, the Ba-sensitive instantaneous current displayed a marked inward rectification and behaved with external K as expected for a pure K+ current, suggesting that under these conditions the only current affected by Ba was iK1. The Ba-sensitive current deceased with time during hyperpolarizations even when high external K was present, indicating that a voltage-dependent inactivation process could be at least in part responsible for the observed current decline.

Animals↗
PubMed1983

Delayed activation of the cardiac pacemaker current and its dependence on conditioning pre-hyperpolarizations.

The activation time course of the pacemaker current if in Purkinje fibres during hyperpolarizations is s-shaped, which requires kinetics more complex than first order. Large, short hyperpolarizations preceding a fixed activating test pulse cause the current trace to shift to the left on the time-axis, as if a delay in if activation were removed, and eventually lead to a current trace which is a simple exponential and activates with no delay during a test pulse. Current traces before and after a relatively short and small prepulse will superimpose after a time translation. Further increasing prepulse amplitude and/or duration gives current traces that cannot be made to superimpose with the test current trace. The channel opening can be described by first order kinetics only if a delay in current activation is introduced.

Animals↗