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R D Nathan

Publications and source records attributed to R D Nathan.

28 records · Page 2Linked to original sources

Sialic acid: regulation of electrogenesis in cultured heart cells.

Removal of up to 50% of the sialic acid from aggregates of 7-day chick embryo heart cells during incubation in a highly purified preparation of neuraminidase resulted in hyperpolarization of the maximum diastolic potential, reduction in the slope of diastolic depolarization leading to slowing of beating, negative shifts of threshold potential and the voltage at which upstroke velocity was maximal, and an initial increase in the action potential overshoot. These effects were opposite to those induced by phospholipase C, a possible contaminant. The modification of electrical properties by neuraminidase is suggested to result from an enhanced influx of calcium ions that might "screen" or bind specifically to internal negative fixed charges and thereby shift the voltage dependence of conductance and kinetic parameters to more negative potentials. This hypothesis is supported by the results above and by greater uptake of 45Ca following release of sialic acid, augmentation of enzyme-induced changes in elevated Ca2+, and the similarity of effects produced by A23187, and inophore which also increased 45Ca uptake. However, other mechanisms cannot be ruled out at the present time.

Action Potentials↗

Voltage clamp analysis of embryonic heart cell aggregates.

The double-microelectrode voltage clamp technique was applied to small spheroidal aggregates of heart cells from 7-d chick embryos. A third intracellular electrode was sometimes used to monitor spatial homogeneity. On average, aggregates were found to deviate from isopotentiality by 12% during the first 3--5 ms of large depolarizing voltage steps, when inward current was maximal, and by less than 3% thereafter. Two components of inward current were recorded: (a) a fast, transient current associated with the rapid upstroke of the action potential, which was abolished by tetrodotoxin (TTX); and (b) a slower inward current related to the plateau, which was not affected by TTX but was blocked by D600. The magnitudes, kinetics, and voltage dependence of these two inward currents and a delayed outward current were similar to those reported for adult cardiac preparations. From a holding potential of -60 mV, the peak fast component at the point of maximal activation (-20 mV) was -185 microA/cm2. This value was about seven times greater than the maximal slow component which peaked at 0 mV. The ratio of rate constants for the decay of the two currents was between 10:1 and 30:1.

Action Potentials↗

In vitro differentiation of a fast Na+ conductance in embryonic heart cell aggregates.

Aggregates of 3-day chick cardiac myocytes, after 2 days of gyration culture, lack a tetrodotoxin-sensitive, fast Na+ conductance. After 2--3 additional days in vitro these aggregates were shown by three different criteria to have developed such a conductance mechanism: (a) action potential upstroke velocities greater than 90 V/sec; (b) suppression of spontaneous activity by tetrodotoxin; and (c) presence of a fast component of inward current recorded during voltage clamp. These membrane properties were similar to those of aggregates derived from 7-day hearts that had developed in ovo. The differentiation of fast Na+ conductance channels was a dependent upon active protein synthesis but not upon the presence of exogenous macromolecules.

Action Potentials↗

Ultraviolet-induced alterations of beat rate and electrical properties of embryonic chick heart cell aggregates.

Embryonic heart cell aggregates were irradiated with ultraviolet light at wavelengths between 260 and 310 nm. Spontaneous beat rate was monitored with the aid of a closed-circuit TV camera and, in separate experiments, electrophysiological changes were assayed by intracellular recording. The characteristic response of 7-day aggregates was an increase in spontaneous beat rate to a maximum plateau level, followed by a rather abrupt cessation of beating. Intracellular recordings during irradiation showed a marked decline in the maximum rate of rise, overshoot, and repolarization phase of the action potential, and a significant change in threshold toward zero. The action spectrum for the termination of beating peaked between 290 and 295 nm; it fell off sharply at longer wavelengths and more slowly at shorter wavelengths. The maximum increase in beat rate was increasingly greater for shorter wavelengths and exhibited no peak in the wavelength range investigated. The sensitivity of aggregates to 295-nm light, as measured by the inverse of irradiation time required to terminate beating, decreased with increasing aggregate size and external potassium concentration, was relatively independent of temperature, and increased with embryonic age. The ultraviolet-induced increase in beat rate and termination of beating are attributed to separate complementary processes, a depolarization of the membrane, and a decline in "fast" sodium conductance.

Action Potentials↗

Spectral analysis of the EEG recorded during stimulation of the human fovea.

Computer spectral analysis was performed on the EEGs of 6 subjects recorded during monocular foveal stimulation. Stimulus wavelength and subjective brightness were varied independently to determine their importance to changes in the ongoing EEG. The contribution of oculomotor control to these effects and the retinal area of their origin were also investigated. The major results were as follows. (1) Stimulation of the fovea reduced the amplitude of the EEG and the coherence between hemispheres at all frequencies, but most dramatically in the alpha band. (2) It increased the variance of EEG amplitudes and widths of spectral peaks in the alpha band and shifted these peaks to lower frequencies. (3) Auto-spectral intensities in the alpha band were enhanced slightly at brightness levels near photopic threshold, but were unaffected by changes in stimulus wavelength. (4) The fovea appeared to be the most effective retinal area in which irradiation attenuated ongoing alpha activity.

Accommodation, Ocular↗

Sialic acid at the surface of myocardial cells during embryonic development.

We tested the hypothesis that the reduction of automaticity during the embryonic development of chick ventricular myocytes is correlated with the number of sialic acid residues at the cell surface. The major findings were twofold. First, the sialic acid content of ventricular tissue fragments declined during the period between 4 and 17 days of development; however, when a 26% reduction of cell surface area was taken into account, the surface density of sialic acid at 7 and 17 days was not significantly different. Second, the sialic acid content of ventricular cell aggregates (after 3 days in gyratory culture) increased during the same two-week period. On the surface of these cells, the density was significantly greater at 17 days than at 7 days, even after a 17% increase in cell surface area had been taken into account. When the developmental increase in sialic acid content was compared with a concomitant decline in aggregate beat rates, we calculated a correlation coefficient of 0.85. Thus, while there could be some relationship between aggregate automaticity and sialic acid content, there appears to be no such correlation for fragments of chick ventricle.

Animals↗