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Biomedical subjects

L F Jaffe

Publications and source records attributed to L F Jaffe.

At least 55 records · Page 3Linked to original sources
PubMed1981

The role of ionic currents in establishing developmental pattern.

This paper reviews a theory of pattern establishment and pattern restoration by endogenous ionic currents. These currents are supposed to be generated by a certain separation of ion leaks and ion pumps in cell membranes. In so far as these currents act back to further this separation, they would be part of a regenerative process that initially establishes positional values. Later in development, particularly in epimorphic regeneration, when positional values are restored or extended, these currents are supposed to leak through sites of discontinuity in such values and thus trigger growth. This paper also reviews the factual evidence for this view: evidence that developmental currents are, indeed, very widespread; evidence in a few cases, particularly in Cecropia follicles and in wounded cavy skin, that they can generate substantial voltage differences or gradients; evidence that comparable artificial fields can move charged macromolecules along cell membranes and polarize cell growth; and direct evidence in a few case, particularly fucoid eggs, Cecropia follicles and regenerating amphibian limbs, that ion currents do, in fact, act back to direct or further development. The paper also presents a particular theory, based upon ionic currents, of the reversal of thyroid cell polarity by serum.

Animals↗
PubMed1981

Control of development by steady ionic currents.

A wide variety of developing systems drive substantial steady ionic currents through themselves. These currents are driven by a certain separation of ion leaks from ion pumps along the membranes of developing cells. Moreover, they seem to be more than epiphenomena. In part they may act back, via self-electrophoresis and/or specific ion gradients, to further segregate the membrane components that drive them; in part they may act to segregate and locally modify other components and thus act as prime agents of differentiation. Among the systems in which evidence for such action has been reported are: 1)Fucoid eggs. There is evidence that early calcium ion currents through these eggs are self-amplifying and induce local growth at the locus of calcium ion entry. 2)Cecropia (insect) follicles. There is evidence that large transfollicular currents maintain enough of a voltage drop between nurse and oocyte cells to help drive macromolecules into the oocytes. 3)Amputated amphibian limbs. There is evidence that large natural stump currents somehow initiate regeneration. 4)Frog embryos. The growth of isolated, embryonic Xenopus neuroblasts and myoblasts can be directed by voltage gradients so small (down to 10 to 30 mV/mm) that they may well exist within the embryo. 5)Wounded mammalian skin. Natural currents through incisions in guinea pig skin establish voltage gradients within the adjoining epidermis that are so large (100 to 200 mV/mm) they may direct wound closure.

Animals↗
PubMed1980

Large and persistent electrical currents enter the transected lamprey spinal cord.

The electrical currents at the surface of the proximal portion of an isolated and transected lamprey spinal cord were measured with an extracellular vibrating probe. Soon after transection, currents of about 0.5 mA/cm2 enter the cut surface of the spinal cord. These currents fall to about a quarter of their initial value within an hour; within the next 2 days they gradually decline from about 100 microA/cm2 to about 4 microA/cm2; they then remain constant up to 6 days posttransection, when the measurements were ended. The pattern of current entry included substantial peaks opposite (and presumably into) the cut ends of giant axons. Response to changes in the ionic composition of the medium indicates that about half of the injury current consists of Na+, and that much of the rest may consist of Ca2+. The measured influx of ions, which adds up to several coulombs per cm2 in a few days, should radically alter the ionic composition of the terminal few millimeters of neural tissue. Thus it may be important in the degenerative and regenerative responses of neurons to axotomy.

Action Potentials↗
PubMed1980

Calcium explosions as triggers of development.

A few years ago, Gilkey et al. showed that the development of medaka fish eggs begins with a free calcium explosion within the cytoplasm. This paper summarizes those findings; provides an interim report on the effects of injecting calcium and hydrogen ion buffers into medaka eggs; reviews recent evidence of similar calcium increases in other activating eggs, as well as sperm and oocytes (Table 1); and attempts to put these explosions in a broader context (Figures 1 and 4).

Animals↗
PubMed1979

Strong electrical currents leave the primitive streak of chick embryos.

The electrical fields above chick embryos were explored with a vibrating probe. These fields indicate that steady currents with exit densities of the order of 100 microamperes per square centimeter leave the whole streak and return elsewhere through the epiblast. The epicenter of these strong exit currents lies near Hensen's node. They are probably pumped into the intraembryonic space by the epiblast and then leak out of the streak because it is a zone of junctional disruption.

Animals↗
PubMed1979

Role of subdermal current shunts in the failure of frogs to regenerate.

Large, uniform, skin-driven currents (20-40 muamp/cm2) leave the ends of limb stumps of post-metamorphic frogs (Rana pipiens) from about the first through the tenth day after amputation. However, right after amputation, while currents of comparable density may leave the periphery of the cut surface, current densities are greatly depressed in the center of this surface. We suggest that this depression is brought about by shunting through the subdermal lymph space (characteristic of anurans but not urodeles); continues in covert form after formation of a wound epithelium; and helps explain the ability of small, imposed currents to initiate frog limb regeneration.

Action Potentials↗
PubMed1979

Neurites grow faster towards the cathode than the anode in a steady field.

We explanted fragments of embryonic chick dorsal root ganglia on to polylysine coated glass and cultured them in a medium containing one unit of nerve growth factor plus enough methylcellulose to give viscosities from 0.01-3,000 poise. We allowed them to grow out in the absence of a field, and then selected explants with halos of neurites which were relatively dense, relatively symmetrical, and practically free of glial cells. These selected explants were then exposed to electrical fields of up to 140 mV/mm for some hours. In media with viscosities of one poise or less, the field some times dragged the central cell mass of an explant towards the anode. However, in cases where the central cell mass did not move, fields of 70-140 mV/mm induced that sector of each neurite halo which faced the cathode to grow out several times faster than the one facing the anode.

Animals↗
PubMed1979

Reduction of sodium dependent stump currents disturbs urodele limb regeneration.

We have asked the question whether the natural electric currents which leave urodele limb stumps are in any way needed for their regeneration. As an initial test, we have greatly reduced such currents in the tiger salamander, Ambystoma tigrinum, by applying 0.5 mM amiloride to the stump skin or by immersion of the animals in sodium depleted media. We have also reduced such currents in the red spotted newt, Notophthalmus viridescens, by such immersion. Limb regeneration in half of the amiloride-treated animals was either entirely blocked or grossly deficient, while the others regenerated normally. Limb regeneration in sodium depleted media was consistently inhibited for some weeks but then recovered. These results are consistent with the hypothesis that stump currents are in some way needed for normal regeneration.

Ambystoma↗
PubMed1979

Large electrical currents traverse developing Ceropia follicles.

An intense (up to 20 muA/cm(2)) steady electrical current enters the anterior or nurse cell end of the growing follicle (or oocyte-nurse cell complex) of the Cecropia moth and is balanced by a more diffuse current leaving elsewhere. In late growth stages, the total transfollicular current is about 100 nA. Moreover, a separate small current, of about 1 nA, seems to leave the furrow between the oocyte and the nurse cells. After the nurse cells collapse, but before shell formation, the transfollicular current is redistributed so that a second relatively localized inward current appears at the posterior pole of the follicle. Thus, at this later stage currents enter both poles of the follicle and leave its sides. Previous measurements, with intracellular microelectrodes, seem to imply a very large (order of 1000 nA) back current across the cytoplasmic bridge between the oocyte and nurse cells. A simple model is presented that attributes the apparent bridge current, and the more directly measured transfollicular and furrow currents, to the action of an ion pump lying within the nurse cell face of the furrow membrane.

Journal Article↗
PubMed1979

Natural H Currents Traverse Growing Roots and Root Hairs of Barley (Hordeum vulgare L.).

With the aid of an extracellular vibrating electrode, natural electric fields were detected and measured in the medium near growing roots and root hairs of barley seedlings. An exploration of these fields indicates that both the root as a whole, as well as individual root hairs, drive large steady currents through themselves. Current consistently enters both the main elongation zone of the root as well as the growing tips of elongating root hairs; it leaves the surface of the root beneath the root hairs. These currents enter with a density of about 2 microamperes per square centimeter, leave with a density of about 0.5 to 1 microampere per square centimeter, and total about 30 nanoamperes.Responses of the natural fields to changes in the ionic composition of the medium as well as observations of the pH pattern in the medium near the roots (made with bromocresol purple) together indicate that much of the current consists of hydrogen ions. Altogether, H(+) ions seem to leak into growing cells or cell parts and to be pumped out of nongrowing ones.

Journal Article↗
PubMed1978

A free calcium wave traverses the activating egg of the medaka, Oryzias latipes.

Aequorin-injected eggs of the medaka (a fresh water fish) show an explosive rise in free calcium during fertilization, which is followed by a slow return to the resting level. Image intensification techniques now show a spreading wave of high free calcium during fertilization. The wave starts at the animal pole (where the sperm enters) and then traverses the egg as a shallow, roughly 20 degrees-wide band which vanishes at the antipode some minutes later. The peak free calcium concentration within this moving band is estimated to be about 30 microM (perhaps 100-1,000 times the resting level). Eggs activated by ionophore A23187 may show multiple initiation sites. The resulting multiple waves never spread through each other; rather, they fuse upon meeting so as to form spreading waves of compound origin. The fertilization wave is nearly independent of extracellular calcium because it is only slightly slowed (by perhaps 15%) in a medium containing 5 mM ethylene glycol-bis[beta-aminoethyl ether]N,N'-tetraacetic acid (EGTA) and no deliberately added calcium. It is also independent of the large cortical vesicles, which may be centrifugally displaced. Normally, however, it distinctly precedes the well-known wave of cortical vesicle exocytosis. We conclude that the fertilization wave in the medaka egg is propagated by calcium-stimulated calcium release, primarily from some internal sources other than the large cortical vesicles. A comparison of the characteristics of the exocytotic wave in the medaka with that in other eggs, particularly in echinoderm eggs, suggests that such a propagated calcium wave is a general feature of egg activation.

Animals↗
PubMed1977

Electrophoresis along cell membranes.

Bioelectric fields may segregate charged components floating in the plasma membranes of cells by a process of electrophoresis along the membrane. Molecules in cell membranes may be sorted to different portions of the cell surface by such electrical gradients. We present here a theory to support this hypothesis.

Cell Membrane↗
PubMed1977

Bioelectricity and regeneration: large currents leave the stumps of regenerating newt limbs.

Electrical currents near regenerating newt limbs were measured with a recently developed vibrating probe. Steady currents with local surface densities of 10 to 100 muA/cm2 or more leave the end of the stump during the first 5-10 days after amputation and are balanced by currents with densities of only 1-3 muA/cm2 that enter the intact skin around the stump. They are immediately dependent upon the entry of sodium ions into this skin and are therefore inferred to be skin-driven. The outward currents are comparable in direction, density, duration, and position to artificially imposed currents previously found sufficient to induce significant regeneration of amputated adult frog limbs. This comparison suggests that the endogenous stump currents play some causal role in initiating regeneration.

Amiloride↗
PubMed1977

Free calcium increases explosively in activating medaka eggs.

We have used the calcium-specific light-emitting protein aequorin to follow changes in free calcium concentration during fertilization and cleavage of eggs from medaka, a fresh-water fish. Aequorin-injected medaka eggs show a very low resting glow before they are fertilized, indicating a low calcium concentration in the resting state. Upon activation by sperm, the calcium-mediated light emission increases to a level some 10,000 times the resting level with a 1 to 2 sec time constant for an e-fold increase, and then slowly retruns to the resting level. Upon activation by the ionophore A23187, the early rise in luminescence is much slower, but once a threshold has been reached the subsequent rise becomes as rapid as the normal sperm-induced response. We infer that the explosive rise in calcium involves calcium-stimulated calcium release, and that a sperm normally triggers this rise by somehow inducing a more modest and localized rise in calcium.

Aequorin↗
PubMed1977

Relations between ameboid movement and membrane-controlled electrical currents.

We have studied the pattern of electrical currents through amebas (mainly Chaos chaos) with an ultrasensitive extracellular vibrating probe. Amebas drive both steady currents and current pulses through themselves. Relatively steady current with an average surface density of 0.1-0.2 muA/cm2 enters the rear quarter of an ameba and leaves its pseudopods. Streaming reversals are preceded by changes in this current pattern and the region with the largest new inward current becomes the new tail. Ion substitution studies suggest that some of the steady inward current is carried by calcium ions. Characteristic stimulated pulses of current sometimes follow the close approach of the vibrating probe to the side of an advancing pseudopod. Such a pulse enters the cytoplasm through a small patch of membrane near the probe (and seems to leave through the adjacent membrane), is usually followed by hyaline cap and then by pseudopod initiation, is calcium dependent, lasts about 5-10 s, and has a peak density of about 0.4 muA/cm2. Spontaneous pulses of similar shape and duration may enter or leave any part of an animal. They are much less localized, tend to have higher peak densities, and occur in physiological salt solutions at about 0.2-4 times per minute. Retraction of a pseudopod is always accompanied or preceded by a spontaneous pulse which leaves its sides.

Amoeba↗