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Biomedical subjects

E Rios

Publications and source records attributed to E Rios.

At least 19 recordsLinked to original sources

Nonlinear charge movement in mammalian cardiac ventricular cells. Components from Na and Ca channel gating.

Intramembrane charge movement was recorded in rat and rabbit ventricular cells using the whole-cell voltage clamp technique. Na and K currents were eliminated by using tetraethylammonium as the main cation internally and externally, and Ca channel current was blocked by Cd and La. With steps in the range of -110 to -150 used to define linear capacitance, extra charge moves during steps positive to approximately -70 mV. With holding potentials near -100 mV, the extra charge moving outward on depolarization (ON charge) is roughly equal to the extra charge moving inward on repolarization (OFF charge) after 50-100 ms. Both ON and OFF charge saturate above approximately +20 mV; saturating charge movement is approximately 1,100 fC (approximately 11 nC/muF of linear capacitance). When the holding potential is depolarized to -50 mV, ON charge is reduced by approximately 40%, with little change in OFF charge. The reduction of ON charge by holding potential in this range matches inactivation of Na current measured in the same cells, suggesting that this component might arise from Na channel gating. The ON charge remaining at a holding potential of -50 mV has properties expected of Ca channel gating current: it is greatly reduced by application of 10 muM D600 when accompanied by long depolarizations and it is reduced at more positive holding potentials with a voltage dependence similar to that of Ca channel inactivation. However, the D600-sensitive charge movement is much larger than the Ca channel gating current that would be expected if the movement of channel gating charge were always accompanied by complete opening of the channel.

Animals

A general procedure for determining the rate of calcium release from the sarcoplasmic reticulum in skeletal muscle fibers.

A general procedure for using myoplasmic calcium transients measured with a metallochromic indicator dye to calculate the time course of calcium release from the sarcoplasmic reticulum in voltage-clamped skeletal muscle fibers is described and analyzed. Explicit properties are first assigned to all relatively rapidly equilibrating calcium binding sites in the myoplasm so that the calcium content (CaF) in this pool of "fast" calcium can be calculated from the calcium transient. The overall properties of the transport systems and relatively slowly equilibrating binding sites that remove calcium from CaF are then characterized experimentally from the decay of CaF following fiber repolarization. The rate of calcium release can then be calculated as dCaF/dt plus the rate of removal of calcium from CaF. Two alternatives are assumed for the component of CaF that is due to fast binding sites intrinsic to the fiber: a linear instantaneous buffer or a set of binding sites having properties similar to thin filament troponin. Both assumptions yielded similar calcium release wave forms. Three alternative methods for characterizing the removal system are presented. The choice among these or other methods for characterizing removal can be based entirely on convenience since any method that reproduces the decay of CaF following fiber repolarization will give the same release wave form. The calculated release wave form will be accurate provided that the properties assumed for CaF are correct, that release turns off within a relatively short time after fiber repolarization, that the properties of the slow removal system are the same during and after fiber depolarization, and that possible spatial nonuniformities of free or bound calcium do not introduce major errors.

Animals

Intramembrane charge movement in frog skeletal muscle fibres. Properties of charge 2.

1. Membrane currents were measured in cut skeletal muscle fibres voltage-clamped in a double Vaseline gap in solutions that had impermeant ions substituted for Na+, K+ and Cl-. The fibres were maintained at a holding potential of 0 mV. Pulses to positive voltages elicited outward currents that were proportional to voltage at all times; these were used to estimate linear capacitive currents, which in turn were used in the construction of non-linear current transients. 2. Large negative-going pulses elicited proportionally larger inward currents that decayed during the pulse with voltage-dependent kinetics. A portion of the non-linear current could be eliminated by solutions containing EGTA, as well as by large negative conditioning pulses of 200 ms or more. This portion was probably an inward Ca2+ current. 3. The non-linear current remaining in EGTA-containing solutions had characteristics of intramembrane charge movement ('charge 2'). This charge depended on voltage according to a two-state Boltzmann function of average parameters Qmax = 47.7 nC/microF, V = -115 mV, K = 21.5 mV (seven fibres). 4. The charge movement current transients were single-exponential decays (after a short rising phase) with time constants (tau) that depended on voltage (V). A single-barrier Eyring rate model described well the dependence of time constant on voltage. This fit permitted an independent estimate of a transition voltage, V, and a slope parameter K related to apparent valence of the mobile particle. The values of V and K that best fitted the kinetic data were close to the corresponding values estimated from the charge vs. voltage distribution. 5. Effective capacitance was measured by the transfer of capacitive charge by a small pulse superimposed on a variable pre-pulse. The capacitance was found to depend on pre-pulse voltage. The voltage dependence of the capacitance was as expected from the properties of charge 2 measured independently in the same fibres. 6. The presence of charge 2, defined as charge that moves in a very negative voltage range, was compared on the same fibres in a depolarized and a normally polarized (holding potential = -100 mV) situation. All fibres had less charge 2 at a holding potential of -100 mV (14 nC/microF average reduction). In these fibres charge 1, explored with pulses from -70 mV to 0 mV, was greater at a holding potential of -100 mV (18 nC/microF average increase).(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials

Simultaneous measurements of Ca2+ currents and intracellular Ca2+ concentrations in single skeletal muscle fibers of the frog.

The relationship between Ca2+ current amplitudes and myoplasmic Ca2+ transients was studied in single muscle fibers. Segments of muscle fibers were voltage-clamped in a double Vaseline gap chamber. Ca2+ transients were measured as an optical signal derived from the interaction between Ca2+ and the dye antipyrylazo III. The cells were maintained at -90 mV. Ca2+ currents were detected at pulse potentials to -50 mV, reached a maximum value at 0 mV, were reduced in size for larger depolarizations, and reversed at about 40 mV. Ca2+ transients were also detected at -50 Mv and progressively increased in size with larger pulse potentials up to 10 mV. Depolarizations to voltages greater than 10 mV did not further increase the size of the transient. The magnitude and time course of transients from 10 to 70 mV were almost identical Ca2+ fluxes into the myoplasm (Ca2+ input fluxes) were calculated from the Ca2+ transients applying a removal model. The size of the input fluxes increased with depolarization up to 0 mV. Between 0 and 70 mV the peak input flux slightly increased, while the flux measured at 200 ms remained unchanged. In conclusion, Ca2+ transients and input fluxes were not reduced during pulses to large positive potentials, even though a drastic reduction of Ca2+ current occurred at these potentials. These observations make it very unlikely that a voltage-dependent Ca2+ entry is the triggering signal for contraction.

Animals

Use of a metallochromic indicator to study intracellular calcium movements in skeletal muscle.

The transient increase in free myoplasmic calcium concentration due to depolarization of a skeletal muscle fibre is the net result of the release of calcium from the sarcoplasmic reticulum (SR) and its simultaneous removal by binding to various sites and by reuptake into the SR. We review here procedures recently developed in this laboratory for empirically characterizing the calcium removal processes in voltage-clamped fibres and for using such characterization to determine the time course of SR calcium release during a depolarizing pulse.

Animals

The inotropic memory of amphibian myocardium.

(1) Experimentally observed changes of contractile force induced by changes in the pattern of stimulation of frog ventricular myocardium were compared with predictions computed on the basis of a model for the contractile conditioning, proposed in a previous paper. (2) For this purpose, two functions (Potentiation and Inhibition) which describe in the model the effect of previous contractions, were determined experimentally. (3) It is shown that the model adequately predicts : force-frequency curve Inotropic Effect Curves at different basal frequencies, effect of the suppression of a contraction in a sequence of definite frequency, frequency-staircases, and strength-interval curves. (4) The formal characteristics of the model are discussed, and it is suggested that the potentiation mechanism results from the recirculation of activator calcium in two types of compartments, from which calcium passes to the myofilaments during the contractions or is lost to the exterior with first order kinetics during the rest period. Possible locations for these compartments are proposed. Various hypothesis on the nature of the inhibitory mechanism are considered.

Animals

The inotropic memory of amphibian myocardium. I.-Identification of two stimultaneous mechanisms and statement of a model.

(1) The effects of previous contractions on the actual contractile strength is studied in strips of toad ventricle. The inotropic effect is quantified by superposing a conditioning contraction to a rhythm of definite frequency, its measure being the difference in strength between a rhythm contraction in the presence and in the absence of the conditioning one. (2) The inotropic effect is studied as a function of the interval between the actual and conditioning contractions. Depressed sections of the curve, associated to shortened action potentials, are detected and excluded. (3) The inotropic effect is always positive at low frequencies, but at higher frequencies and long intervals it becomes negative. (4)In high calcium concentration the inotropic effect is always negative and does not depend on frequency. Morever, the joint effect of two previous contractions is equal to the sum of the individual effects of each one. (5) The results are interpreted in terms of two independent elementary processes, one of which potentiates whereaas the other inhibits the strength of contraction. The former disappears in high calcium. Assuming some simple properties for these processes a mathematical expression has been achieved. This expression describes the inotropic effect of any sequence of contractions as a function of intervals involved.

Action Potentials

Relationship of maternal and infant iron stores as assessed by determination of plasma ferritin.

Using plasma ferritin derminations, iron stores have been evaluated at the end of pregnancy in 26 women and followed sequentially in their healthy, full-term infants. It has been shown that the iron storage status of the mother does not affect the iron status of the infant. Determinations of plasma ferritin in the infants have demonstrated that by 6 months of age the iron status of the infant reflects the adequacy of the dietary intake of iron. In the absence of effective iron supplementation during the first six months, plasma ferritin levels fall to low levels, indicating the depletion of iron stores in the infant.

Adult

The absorption of iron as supplements in infant cereal and infant formulas.

The absorption of iron was measured from isotopically tagged salts used in supplementing infant cereals and as the iron supplement in cow's milk and soy-based formulas. Iron as sodium iron pryophosphate and ferric orthophosphate were poorly absorbed from infant cereal (mean, smaller than 1.0%) and thus are not dependable sources of iron to meet the nutritional needs of infants. Reduced iron of very small particle size and ferrous sulfate when added to cereal was absorbed to a greater extent (mean, 4.0% and 2.7% respectively). For technical reasons, these two forms of iron had not been added to commercial cereal products because of discoloration, distribution problems of the iron in the product, and shortened shelf life. Therefore, at the present time, iron supplementation of infant cereals with sodium iron pyrophosphate, ferric orthophosphate, and reduced iron of large particle size does not provide a predictable and available source of iron to meet the needs of infants. Supplemental iron as ferrous sulfate in milk- and soy-based formulas gave a mean absorption of 3.4% and 5.4%. The iron supplements in these formulas can essentially meet the needs for dietary iron of healthy infants.

Animals

Stereotactic hypothalamotomy for behaviour disorders.

Posterior hypothalamotomy is a relatively simple stereotactic procedure. The radiological determination of the target and its physiological corroboration by electrical stimulation are accurate. The lesions have always been made in the site of maximum sympathetic response. In this respect, the cardiovascular changes (hypertension and tachycardia), which are always elicited from a more restricted area, are of particular importance. Depth recordings, however, have been less useful. Undesirable side-effects, if present, were mild and transitory. There was no postoperative intelligence deficit, at least with the standard tests.

Adolescent