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Biomedical subjects

F Conti

Publications and source records attributed to F Conti.

At least 109 records · Page 6Linked to original sources

Pressure dependence of sodium gating currents in the squid giant axon.

Asymmetric displacement currents, Ig, were measured in squid axons at different hydrostatic pressures, P, up to 60 MPa. Potassium and sodium currents were abolished by intracellular Cs+ and TEA+, by extracellular Tetrodotoxin (TTX), and by Na+ substitution with Tris+. The time course of Ig became progressively slower with increasing pressure, and the amplitude decreased. With appropriate scaling in time and amplitude, Ig records at any given P could be made to superimpose very well with those obtained at atmospheric pressure. The same scaling factors yielded a good superposition of all records obtained for voltage steps to membrane potentials in the range -30 to +42 mV. The ratio between the amplitude and time factors was larger than unity and increased with P, indicating a progressive decrease (up to 35% at 60 MPa) of the total charge displaced, Q, with no significant change in its voltage dependence. The time-scaling factor increased exponentially with P, as expected if all the steps involved in the opening of a sodium channel, and producing a major charge redistribution, have the same activation volume, delta V not equal to g approximately 17 cm3/mol. This value is roughly one-half of that characterizing the pressure dependence of sodium current activation, suggesting that some late, rate-limiting step in the opening of sodium channels has a large activation volume without being accompanied by an easily detected charge movement. Part of the decrease of Q with pressure could be attributed to an increase in sodium inactivation. However, we cannot exclude the possibility that there is a reversible reduction in the number of fast activating sodium channels, similar to the phenomenon that has been reported to occur at low temperatures (Matteson and Armstrong 1982).

Animals

Callosal mechanism for the interhemispheric transfer of hand somatosensory information in the monkey.

The retrograde transport of horseradish peroxidase (HRP) was combined with extracellular microelectrode recording from single and multiple-neurones to study the anatomical and functional organization of the callosal connections of the hand sensory projection field in the parietal operculum of monkeys (Macaca Irus). In 3 animals anaesthetized with ketamine, a single injection of HRP (0.5 microliter) was delivered into the cortex forming the upper bank of the sylvian sulcus at a site where neuronal responses to somatic sensory stimulation of the hand were recorded. In the ipsilateral hemisphere, retrogradely HRP-labelled cells were found in the cortex of the post-central gyrus and in the thalamic nuclei ventralis posteroinferior and pulvinar oralis. In the contralateral hemisphere HRP-labelled neurones were present in the opercular cortex lying dorsal, and slightly caudal, to the posterior pole of the insula. Few scattered callosal neurones were also found in the post-central gyrus. In 3 other animals, multiple injections (5-8; 0.5 microliter each) of HRP were performed in the parietal operculum. In the ipsilateral hemisphere, retrogradely labelled cells were present in the post-central gyrus and in the following thalamic nuclei: ventralis posteroinferior, pulvinar oralis and medialis, ventralis posteromedialis and posterior complex. Few labelled cells were also present in the ventral part of the nucleus ventralis posterolateralis. In the contralateral hemisphere, numerous callosal cells were labelled with HRP. These cells were found, with regional variations in density, in wide regions of the buried and exposed cortex of the parietal operculum and in the post-central gyrus. These 3 monkeys were subjected to microelectrode mapping experiments (N2O and halothane anaesthesia) to explore the peripheral receptive fields of neurones in the parietal operculum and post-central gyrus contralateral to the injected side. HRP labelled callosal neurones were found in regions of the second and first somatosensory cortical areas which also contained units driven from the contralateral hand.

Animals

Non-stationary fluctuations of the potassium conductance at the node of ranvier of the frog.

Potassium currents were recorded from voltage-clamped nodes of isolated, myelinated axons of Rana pipiens. Nodes were maintained in a modified Ringer solution containing tetrodotoxin to block sodium current and 47.5 mM-potassium to minimize effects of extracellular potassium accumulation. Voltage protocols included depolarizing pulses lasting a few milliseconds to several seconds. Fluctuations about the ensemble average of the current were characterized in terms of non-stationary variance and autocovariance. The fluctuations had a Gaussian amplitude distribution and were virtually free of contaminations from systematic variations of the membrane current. Corrections for background noise were based on measurements done while potassium current was blocked with tetraethylammonium, and on simulations of extrinsic current fluctuations expected to arise from noise in the actual membrane voltage. The fluctuations were attributed to variations of nodal potassium conductance, since they were absent at the reversal potential of the potassium current and at membrane voltages that do not activate potassium current. Covariances indicated that voltage steps that reversed a macroscopic potassium current also reversed the sign of the fluctuation. Plots of the conductance variance versus the mean potassium conductance were generated from both the activation and deactivation (tail) phases of the potassium currents at various voltages between -80 and +70 mV. When the current was activated by a small depolarization (-50 mV) the trajectories from both phases were indistinguishable and were fitted by the parabola expected for a single population of channels with only one open-channel conductance. Apparent single-channel conductance from the early activation phase averaged 24 pS and was not significantly voltage dependent. In contrast, experiments with large depolarizations (+10 to +70 mV) gave significantly different variance--mean trajectories during activation and deactivation and these trajectories were poorly fitted by parabola. This result indicates that the fluctuations reflect several populations of channels and/or a population of channels that can have several levels of non-zero conductance. Projections of the fluctuation covariance showed long correlations, as well as the rapidly decaying component expected from the activation gating of channels. A slow fluctuation arose at a time slightly later than the rise of potassium current, spanned the entire length of brief depolarizations, and extended up to 880 ms during long depolarizations.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials

Axonal branching in the periaqueductal gray projections to the thalamus: a fluorescent retrograde double-labeling study in the cat.

The double-labeling technique based on the retrograde axonal transport of fluorescent tracers (Evans blue, EB; Fast blue, FB; Nuclear yellow, NY) was used in the cat in order to investigate the occurrence of axonal branching in the periaqueductal gray (PAG) projections to some thalamic nuclei (n. ventralis postero-lateralis, VPL; n. ventralis postero-medialis, VPM; n. parafascicularis, Pf). In a first group of cats, FB and EB were injected, respectively, within the right and left VPM. In another two groups of cats, FB injections into Pf were combined with either EB or NY injections within VPL or VPM. Double-labeled neurons were found within the PAG only in the animals of the first group. The present results show that some PAG neurons project bilaterally to VPM by means of axons collaterals.

Animals

Periaqueductal grey projection to the ventrobasal complex in the cat: an horseradish peroxidase study.

Horseradish peroxidase (HRP) was injected within the thalamic ventrobasal complex of 14 cats. The aim was to ascertain whether the periaqueductal grey matter (PAG) sends fibres to this complex. Retrogradely labelled cells were found within the PAG following HRP delivery either in the nucleus ventralis posterolateralis (VPL) or ventralis posteromedialis (VPM). PAG-VPL projection is only ipsilateral and arises mainly from lateral PAG, PAG-VPM projection is bilateral and originates from latero-ventral regions of the central grey. The hypothesis that PAG might control the activity of ventrobasal nociceptive neurones is proposed.

Afferent Pathways

[Anatomic demonstration of axon collaterals of the periaqueductal gray formation and the ventrobasal thalamic nuclei of both sides].

In 4 adult cats the left and right thalamic nucleus VPM have been injected with fluorescent substances, Evans Blue and Fast Blue in order to ascertain whether PAG cells send bifurcated axons to the thalamic nuclei of both sides. The results confirm previous studies on the PAG-VPM connections performed in this laboratory by using HRP technique, and demonstrate, within the PAG, the presence of a good number of double-labeled cells (stained by both E.B. and F.B.) intermingled with single-labeled cells, stained either by E.B. or F.B. The double-labeled cells might represent the anatomical substrate of a possible bilateral analgesic mechanism in the trigeminal region.

Animals

Reversible electrical breakdown of squid giant axon membrane.

Charge pulse relaxation experiments were performed on squid giant axon. In the low voltage range, the initial voltage across squid axon membrane was a linear function of the injected charge. For voltages of the order of 1 V this relationship between injected charge and voltage across the membrane changes abruptly. Because of a high conductance state caused by these large electric fields the voltage across the membrane cannot be made large enough to exceed a critical value, Vc, defined as the breakdown voltage, Vc has for squid axon membrane a value of 1.1 V at 12 degrees C. During breakdown the specific membrane conductance exceeds 1 S. cm-2. Electrical breakdown produced by charge pulses of few microseconds duration have no influence on the excitability of the squid axon membrane. The resealing process of the membrane is so fast that a depolarizing breakdown is followed by the falling phase of a normal action potential. Thus, membrane voltages close to Vc open the sodium channels in few microseconds, but do not produce a decrease of the time constant of potassium activation large enough to cause the opening of a significant percentage of channels in a time of about 10 mus. It is probable that the reversible electrical breakdown is mainly caused by mechanical instability produced by electrostriction of the membrane (electrochemical model), but the decrease in the Born energy for ion injection into the membrane, accompanying the decrease in membrane thickness, may play also an important role. Because of the high conductance of the membrane during breakdown it seems very likely that this results in pore formation.

Action Potentials

[Pelviperineal recurrences in surgery of rectal carcinoma].

A series of pelviperineal recurrences after perineal-abdominal amputation of the rectum and after anterior resection is examined. Involvement of the rectal wall, the biological behaviour of the tumour, and lymphatic diffusion represent the main causes of recurrence. In some instances, the choice of anterior resection in the treatment of middle rectum carcinoma may constitute a risk factor.

Aged

Electron spin resonance of growing normal and virus-transformed cells.

A g = 2.003 ESR signal, attributed to a free radical localized in HeLa cell nuclei and mitochondria but absent in membranes and cytoplasm, has been studied as a function of the culture growth cycle in normal (NRK and 3T3) and virus transformed (NRK/RSV and 3T3/SV40) cells. For both these cell pairs, the signal is higher during the "lag" stage and lower during the "growth" stage. The average specific intensity of the signal in normal cells is about twice that in virus-transformed cells. However, the maximal point of resonance during the lag state is higher in transformed cells than in normal ones. The lag stage in NRK and NRK/RSV cells is much longer than in 3T3 and 3T3/SV40 cells, while the maximal value of the g = 2.003 ESR signal occurs, early in the lag stage of 3T3 and 3T3/SV40 cells and late in the lag stage of NRK and NRK/RSV cells.

Animals