Biomedical subjects

A Pignatelli

Publications and source records attributed to A Pignatelli.

9 recordsLinked to original sources

PubMed1999

Calcium-independent release of neurotransmitter in the retina: a "copernican" viewpoint change.

The release of synaptic transmitter in chemical synapses is brought about by Ca2+ influx through voltage-dependent Ca2+ channels opened by depolarisation of presynaptic terminals. However, in some preparations transmitter release persists or increases in low-Ca2+ media, and it has therefore been proposed that transmitter release could also occur through a Ca2+-independent, carrier mediated process. In particular it has been suggested that this may be the case for synaptic transmission between photoreceptors and second order neurones of the vertebrate retina. From our recent experiments on synaptic transmission from photoreceptors to horizontal cells of turtle and salamander retinas, it appears that lowering extracellular Ca2+ can actually promote Ca2+ influx through voltage-activated Ca2+ channels via a modification of surface potential of plasma membranes. On the basis of this apparently paradoxical effect of low Ca2+ media, it is possible to reaccommodate the so-called Ca2+-independent release within the framework of Ca2+-dependent synaptic transmission without invoking unconventional mechanisms.

Animals↗

PubMed1999

Manipulation of synaptic sign and strength with divalent cations in the vertebrate retina: pushing the limits of tonic, chemical neurotransmission.

At the first synaptic level of the vertebrate retina, photoreceptor light responses are transmitted to second order neurones through a chemical synapse based on a tonic release of neurotransmitter modulated by graded changes of presynaptic potential. The possibility that such synapses could work through a Ca2+-independent process had been proposed by previous authors, based on the persistence of transmission process in low Ca2+ media containing Co2+ or Ni2+ ions. Recently, we were able to explain these results within the framework of the classical calcium-hypothesis of synaptic transmission by taking into account the modifications of presynaptic surface potential brought about by changes of divalent cation concentrations. Here we report data showing how a surface-charge hypothesis could account for several apparently paradoxical effects of divalent cation manipulations such as: the enhancement of neurotransmitter release induced by low Ca2+ media; the transmission "unblocking" effect of Zn2+, Co2+ and Ni2+; and the reversal of transmission polarity induced by application of low Ca2+ media containing Cd2+ or Mg2+ ions.

Ambystoma↗

PubMed1999

Resistance of retinal extracellular space to Ca2+ level decrease: implications for the synaptic effects of divalent cations.

Ion-sensitive microelectrodes were used to measure the variations of [Ca2+]o induced by application of low Ca2+ media in the superfused eyecup preparation of the Pseudemys turtle. The aim of the experiments was to evaluate the possibility, suggested by previous studies, that in the deep, sclerad, layers of the retina [Ca2+]o may remain high enough to sustain chemical synaptic transmission even after prolonged application of low-Ca2+ saline. It was found that, at depths of 100-200 micron from the vitreal surface, [Ca2+ ]o did not fall below 1 mM even after application for periods of 30-60 min of nominally Ca2+-free media, and it was >0.3 mM after 30-min application of media containing EGTA and with a Ca2+ concentration of 1 nM. Previous studies in isolated salamander photoreceptors have shown that a reduction of [Ca2+ ]o to 0.3-1.0 mM may result in a paradoxical increase of Ca2+ influx into synaptic terminals due to the reduced screening of negative charge on the external face of the plasma membrane. On the basis of these results, the persistence or enhancement of synaptic transmission from photoreceptors to horizontal cells observed in various retinas treated with low-Ca2+ media may be accounted for within the classical Ca2+-dependent theory of synaptic transmission without invoking a Ca2+-independent mechanism.

Animals↗

PubMed1997

Retinal horizontal cells: old cells, old experiments, new results.

The study of neural interactions in the vertebrate retina carried out after the pioneering studies of Svaetichin has provided important information on the functioning of nerve circuits in the central nervous system. Recently we have investigated the effects of changes of divalent cation concentration on the synaptic transmission between cones and horizontal cells of the turtle retina. Our results seemed apparently in contrast with the classical Ca2(+)-hypothesis of chemical synaptic transmission. Application of low Ca2+ media resulted in a recovery of synaptic transmission after application of divalent cations such as Ca2+, Zn2+ and Ni2+ traditionally considered as Ca2+ channel antagonists. Moreover, in the absence of exogenous divalent cations, low Ca2+ could result in an increase of transmitter release particularly if Mg2+ was omitted from the perfusing medium. These apparently paradoxical results can be reconciled with the postulates of the Ca2(+)-hypothesis of synaptic transmission by taking into account the effects of divalent cations on the fixed charges present at the external surface of cell membrane. It is possible that a similar interpretation could also account for the so-called "Ca2(+)-independent" transmission in other structures of the nervous system.

Animals↗

PubMed1996

Low-calcium-induced enhancement of chemical synaptic transmission from photoreceptors to horizontal cells in the vertebrate retina.

According to the classical calcium hypothesis of synaptic transmission, the release of neurotransmitter from presynaptic terminals occurs through an exocytotic process triggered by depolarization-induced presynaptic calcium influx. However, evidence has been accumulating in the last two decades indicating that, in many preparations, synaptic transmitter release can persist or even increase when calcium is omitted from the perfusing saline, leading to the notion of a "calcium-independent release" mechanism. Our study shows that the enhancement of synaptic transmission between photoreceptors and horizontal cells of the vertebrate retina induced by low-calcium media is caused by an increase of calcium influx into presynaptic terminals. This paradoxical effect is accounted for by modifications of surface potential on the photoreceptor membrane. Since lowering extracellular calcium concentration may likewise enhance calcium influx into other nerve cells, other experimental observations of "calcium-independent" release may be reaccommodated within the framework of the classical calcium hypothesis without invoking unconventional processes.

Ambystoma↗

PubMed1996

Calcium-independent synaptic transmission: artifact or fact?

The release of neurotransmitters at classical chemical synapses occurs via Ca2+ influx through voltage-dependent Ca2+ channels, which are opened following depolarization of presynaptic terminals. However, owing to a persistence or increase in the amount of transmitter released in preparations containing low concentrations of Ca2+, it has been proposed that transmitter release could also occur through a Ca(2+)-independent, carrier-mediated process. On the other hand, lowering extracellular [Ca2+] can actually promote Ca2+ influx through voltage-activated Ca2+ channels via a modification of the surface potential of plasma membranes. Therefore, the proposed Ca(2+)-independent transmitter release could be re-accommodated within the framework of the Ca2+ hypothesis of synaptic transmission by taking into account the surface-charge effects.

Artifacts↗

PubMed1994

[The effects of sublingual nifedipine on isometric stress in patients with severe aortic insufficiency. An acute hemodynamic study].

We studied the acute hemodynamic effects of nifedipine (N) on handgrip test (Hg) in 10 patients with aortic regurgitation in II NYHA functional class. In basal condition (B) we found a significant increase of mean aortic pressure (AoPmean) in all patients after Hg (101 +/- 9.72 versus 110.3 +/- 6.42 mmHg; p < 0.05). Hg did not induce significant changes of AoPmean after N. Hg increased left ventricular end-diastolic pressure (LVEDP) from 13.3 +/- 6.4 to 20.5 +/- 9.9 mmHg (p < 0.01) before N and from 9.7 +/- 3.2 to 12.8 +/- 5.5 mmHg after N (NS). LVEDP measured during Hg after N showed lower values than those measured before N (12.8 +/- 5.5 versus 20.5 +/- 9.9 mmHg; p < 0.01). Cardiac index (CI) increased by Hg in B (3.7 +/- 0.7 versus 4.0 +/- 1.1 L/min/m2; NS) and after N (4.5 +/- 0.7 versus 4.9 +/- 0.9 L/min/m2; NS). CI increased significantly after N at rest (3.7 +/- 0.7 versus 4.5 +/- 0.7 L/min/m2; p < 0.01) and during Hg (4.0 +/- 1.1 versus 4.9 +/- 0.9 L/min/m2; p < 0.01). The left ventricular stroke work index (LVSWI) decreased during Hg from 74.4 +/- 20.6 to 71.2 +/- 20.0 g.m/m2; NS. N caused an increase at rest to 81.4 +/- 22.5 g.m/m2; NS. LVSWI increased significantly during Hg to 83.5 +/- 26.2 g.m/m2; p < 0.05. Systemic arterial resistances (SAR) significantly decreased after N at rest (1,086.8 +/- 280.8 versus 843.5 +/- 133.1 dyne.s.cm-5; p < 0.01), but increased in B during Hg to 1,220.9 +/- 350.7 dyne.s.cm-5; p < 0.05. A significant reduction of SAR values was observed alter N during Hg (1,220.9 +/- 350.7 versus 838.9 +/- 139.9 dyne.s.cm-5; p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗

PubMed1993

[The acute and 24-hour modifications to the atrial natriuretic factor in patients who have undergone mitral valvuloplasty. The hemodynamic and echocardiographic correlations].

BACKGROUND: The recent introduction of percutaneous transvenous mitral valvuloplasty (PTMV) for the treatment of mitral stenosis (MS) has provided a unique human model for the study of short-term changes in ANF secretion before and after a reduction in left atrial pressure. This study was designed to investigate the effect of a short-term reduction in left atrial pressure and volume, as determined by echocardiographic study, on ANF and other neurohumoral factor plasma levels (renin and aldosterone). MATERIALS AND METHODS: 10 patients in III FC NYHA, with normal sinus rhythm and MS underwent PTMV. Hemodynamic parameters were measured immediately before and after (20-30 minutes) PTMV. Plasma levels of ANF, aldosterone and plasma renin activity (PRA) were obtained before (24 h) and after (2 h and 24 h) valvuloplasty; echocardiographic left atrial size before (24 h) and 24 h after PTMV. RESULTS: Immediately after PTMV mean left atrial (LA) pressure decreased from 22.3 +/- 6.8 mmHg to 10.0 +/- 2.4 mmHg (p < 0.01); mitral valve area (MVA) increased from 0.99 +/- 0.28 cm2 to 2.17 +/- 0.26 cm2 (p < 0.01). 24 hours after PTMV on echocardiography, LA systolic volume decreased from 59.5 +/- 16.9 cm3 to 42.3 +/- 8.3 cm3 (p < 0.01), LA diastolic volume from 82.6 +/- 15.8 cm3 to 66.5 +/- 12.6 cm3 (p < 0.01), and LA diameter from 48.1 +/- 7.5 mm to 39.2 +/- 4.4 mm (p < 0.01). ANF plasma levels before PTMV were 64.0 +/- 36.9 fmol/ml; 2 and 24 hours after PTMV they fell to 34.2 +/- 21.6 fmol/ml (p < 0.01) and to 20.3 +/- 21.0 fmol/ml (p < 0.01), respectively. PRA values were 15.7 +/- 13.2 ng/ml/h before PTMV; 2 and 24 hours after PTMV they increased to 17.5 +/- 23.2 ng/ml/h (NS) and to 22.3 +/- 16.8 ng/ml/h (p < 0.01). The aldosterone plasma levels were 43.2 +/- 27.9 ng/dl before PTMV and 47.3 +/- 35.8 ng/dl (NS) and 45.3 +/- 28.0 ng/dl (NS) 2 and 24 hours after PTMV. CONCLUSIONS: These results indicate that LA "de-stretching" due to the MVA increase and LA pressure decrease, leads to an abrupt reduction of ANF secretion. According to other studies, PRA increases immediately after PTMV, with a further increase 24 hours after PTMV.

Adult↗

PubMed1981

Poor prophylactic lithium response due to antidepressants.

50 manic-depressive patients with rapid cycles received lithium for more than 1 year, during depression they received antidepressant drugs. Response was poor in 36, partial in 6, and good in 8. 21 of the poor responders were persuaded to endure depression without antidepressants; anxiolytics were allowed, 15 stabilized after the end of the untreated depression or after a few milder, shorter episodes; 4 improved partially; 2 were unchanged. 15 other rapid cycle patients started on lithium and stopped antidepressants at the same time. Response was good in 13, partial in 1, and poor in 1. Patients with a course of depression-hypomania (or mania)-free interval also responded poorly to prophylactic lithium when the depression was treated with antidepressants. They responded well when antidepressants were withdrawn. Antidepressants often cause or accentuate a switch from depression to hypomania or mania, and temporary refractoriness to lithium of the hypomania or mania. In this way lithium fails to prevent depression.

Antidepressive Agents↗