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Biomedical subjects

J I Hubbard

Publications and source records attributed to J I Hubbard.

At least 73 records · Page 4Linked to original sources
PubMed1972

On the inhibition of muscle contraction caused by exposure to hypertonic solutions.

The evidence supporting a site of inhibition of excitation contraction (E-C) coupling near the plasma membrane (the "glycerol effect," the K(+)-potentiating effect) for muscle in hypertonic solution was reinvestigated. It was found, using whole frog sartorii, that there was a rehydration of muscle soaked in glycerol Ringer after 30 min and a large swelling (to 140% after 1 hr soaking) upon return of the muscle to normal Ringer, suggesting that significant amounts of glycerol enter the fibers during this time. While contrary to the original report of the glycerol effect, this finding was consistent with other studies involving the use of single fibers. Also reexamined was the potentiating effect of K(+) on the hypertonic inhibition of muscle contraction. It was found that muscles exposed to this KCl pretreatment swell so that they are less dehydrated in hypertonic solutions, thus accounting for the observed potentiation. After being treated instead with a K(2)-tartrate Ringer solution, muscles did not swell and, as determined with twitch recordings, did not display any potentiation in hypertonic solutions-even though the [K(+)] was higher than an osmotically equivalent KCl solution. The evidence was thus consistent with alternative hypotheses in which inhibition of contraction occurs at a later stage in E-C coupling or involves the contractile process itself.

Animals↗
PubMed1971

The effect of temperature change upon transmitter release, facilitation and post-tetanic potentiation.

1. End-plate potentials (e.p.p.s) and miniature end-plate potentials (m.e.p.p.s) were intracellularly recorded from rat diaphragm phrenic nerve preparations in vitro at temperatures between 7 degrees and 40 degrees C.2. The quantal content of e.p.p.s and the frequency of m.e.p.p.s showed broadly similar relationships with temperature, with maxima about 20 degrees and above 39 degrees C.3. Analysis of the change in e.p.p. quantal content showed that the maximum about 20 degrees C was accompanied by a similar maximum of p, the probability of release of quanta. The maximum above 39 degrees C was associated with a rise in n, a presynaptic store of material needed for release.4. The rate at which transmitter could be mobilized was linear in an Arrhenius plot with an apparent activation energy of 25 kcal deg(-1).5. Facilitation and post-tetanic potentiation (PTP) were shown to be entirely attributable to changes in p.6. It is suggested that facilitation and PTP have a common basis and that the (temperature-dependent) rate of Ca removal from intracellular sites at which it exerts its action is as important a determinant of the magnitude of quantal release as is the amount of Ca combining with these sites.

Activation Analysis↗
PubMed1968

On the mechanism by which calcium and magnesium affect the spontaneous release of transmitter from mammalian motor nerve terminals.

1. The frequency of miniature end-plate potentials (m.e.p.p.s) was recorded from neuromuscular junctions in rat diaphragm phrenic nerve preparations in vitro after preparations had soaked in solutions containing Ca in concentrations between 10(-10) and 10(-2)M and a similar range of [Mg].2. Ethylenediamine tetra-acetate (EDTA) and ethyleneglycol bis (beta-aminoethyl ether) tetra-acetate (EGTA) buffers were added to prepare solutions with [Ca] and [Mg] below 10(-4)M. A computer program was used to estimate the free [Ca(2+)] in these solutions, and it was shown that the effects of Ca could be attributed to the free [Ca(2+)] in the bathing solution.3. M.e.p.p.s could still be detected without difficulty after soaking preparations for 6-8 hr in solutions containing EDTA or EGTA buffers and no added Ca. The basal frequency was unchanged upon exhibition of Ca in concentrations up to 10(-5)M and/or Mg in concentrations up to 10(-3)M.4. Ca in concentrations of and above 10(-4)M accelerated m.e.p.p. frequency from the basal level. This effect reached a maximum in [Ca] of 10 mM and raising the [Ca] above this level did not further change frequency. These effects were explained by the combination of Ca molecules with a nerve terminal receptor site. It was postulated that this combination allosterically activated the spontaneous release mechanism.5. Mg could accelerate m.e.p.p. frequency in the absence of added Ca. The interactions of Ca and Mg upon m.e.p.p. frequency indicated that Ca and Mg competed for the same sites.6. Raising the [H(+)] of the bathing medium accelerated m.e.p.p. frequency. This effect was thought to be exerted partly by combination with the same receptor sites as Ca and Mg and partly by variation of the ionization of the CaCl(2) of the bathing solution.

Acetates↗
PubMed1968

The effects of depolarization of motor nerve terminals upon the release of transmitter by nerve impulses.

1. Depolarizing currents were applied to motor nerve terminals in the rat phrenic nerve-diaphragm muscle preparation in vitro.2. During the passage of depolarizing currents the amplitude of the presynaptic nerve action potentials and of end-plate potentials (e.p.p.s) was reduced in proportion to the current strength.3. The reduction in e.p.p. amplitudes was shown to be due to a reduction in the number of quanta released.4. An excess of Mg ions or the previous application of a hyperpolarizing current could prevent the reduction of e.p.p. amplitudes and quantal contents by depolarizing current.5. Depolarizing current application prevented later hyperpolarizing currents affecting e.p.p. amplitudes.

Action Potentials↗
PubMed1968

Evidence for the vesicle hypothesis.

1. The relationship of synaptic vesicles to the synaptic cleft was examined with the electron microscope at neuromuscular junctions in the rat diaphragm before and after bathing the preparation in a physiological salt solution for 2 hr.2. A population of vesicles was defined which appeared to ;touch' the axoplasmic membrane. These vesicles were found to be aggregated adjacent to axoplasmic densities which lay opposite the mouths of post-synaptic junctional folds.3. Soaking in the salt solution and modifications of this solution increased the proportion of folds opposed by presynaptic densities with associated vesicles.4. Soaking in solutions with 20 mM-KCl depleted both the specific vesicle population and the whole population of terminal vesicles. The effect was shown in paired experiments to be a specific effect of the 20 mM-KCl, and it was prevented by a concomitant increase of the bathing MgCl(2) concentration.5. Soaking in solutions with a raised osmotic pressure reduced the specific but not the general vesicle population.6. It is suggested that these observations support the vesicle hypothesis and that the specific vesicle population forms part of a feed-back mechanism adjusting transmitter synthesis and mobilization to the rate of release of transmitter.

Acetylcholine↗
PubMed1968

On the mechanism by which calcium and magnesium affect the release of transmitter by nerve impulses.

1. The relationship between the quantal content of end-plate potentials (e.p.p.s) and the bathing [Ca] and [Mg] was determined at neuromuscular junctions in the rat diaphragm in vitro.2. E.p.p.s were recorded intracellularly from preparations exposed to solutions with [Ca] between 0.05 and 10 mM and [Mg] between 0.1 and 12.5 mM. The quantal content of e.p.p.s was increased by raising the [Ca] over this range and decreased by raising the [Mg]. There appeared to be competition of Mg with Ca at three sites in the nerve terminal membrane.3. A kinetic scheme based on competition of Ca and Mg at three sites could quantitatively explain the effects of Ca and Mg upon the quantal content of e.p.p.s and also the effects of these ions upon miniature end-plate potential frequency.

Acetylcholine↗
PubMed1968

An examination of the effects of osmotic pressure changes upon transmitter release from mammalian motor nerve terminals.

1. When the frequency of miniature end-plate potentials (m.e.p.p.s) was measured at neuromuscular junctions in rat diaphragm nerve preparations in vitro bathed in solutions having osmolarities between 200 and 700 m-osmoles/l. it was found that m.e.p.p. frequency was transiently increased by exposure to osmotic gradients exceeding 75 m-osmoles/l., and then declined, within 1 hr, to a steady level slightly higher than the control level of frequency. Smaller osmotic gradients caused a maintained increase in m.e.p.p. frequency. E.p.p. quantal content was initially increased and later profoundly decreased upon exposure of preparations to solutions with an osmotic pressure of 500 or 600 m-osmoles/l. but was unaffected by less hypertonic solutions.2. Variation of the Ca or Mg content of the bathing solutions did not alter these effects of osmotic pressure on the early transient increase in m.e.p.p. frequency or e.p.p. quantal content but affected the late steady increase in m.e.p.p. frequency.3. The value of the transient increase in m.e.p.p. frequency was exponentially related to the osmotic gradient in the range 0-300 m-osmoles/l. with a Q(10) of 1.95 (range 11-34 degrees C). Greater osmotic gradients did not further increase m.e.p.p. frequency. Variation of the ionic strength of the bathing medium did not influence osmotic effects upon frequency.4. The discrepancy between the effects of osmotic gradients upon spontaneous and nerve-impulse induced transmitter release was explained by an occlusion of the osmotic effects by depolarization of nerve terminals. Time-course studies showed that in the presence of 20 mM-KCl the m.e.p.p. frequency increase in response to an increase in osmotic pressure was small and was followed by a reduction in frequency to below control levels while osmotic pressure changes had no immediate effect upon m.e.p.p. frequency in solutions containing 30 mM-KCl.5. It was concluded that increased osmotic gradients could release transmitter by a mechanism independent of Ca and of nerve terminal depolarization.6. It is suggested that the initial transient effects of changes of osmotic gradient upon transmitter release are related to flow of water through the nerve terminal membrane, while the later effects are related to nerve terminal volume changes.

Animals↗
PubMed1967

Origin of synaptic noise.

The poison from puffer fish, tetrodotoxin, was applied to the kitten spinal cord. This application greatly reduced the synaptic noise recorded from lumbar motoneurons. The noise is largely evoked by nerve impulses.

Animals↗
PubMed1966

The origin of the post-tetanic hyperpolarization of mammalian motor nerve terminals.

1. Motor nerve terminals in magnesium-poisoned rat hemidiaphragm-phrenic nerve preparations in vitro were stimulated with short depolarizing pulses of approximately threshold strength and the evoked antidromic responses recorded from the phrenic nerve. The percentage of these 1/sec or 0.5/sec stimuli to which there was no antidromic response was used as a quantitative measure of the terminal excitability. After standard tetanic stimulation (1000 impulses at 100/sec) the excitability of the terminals was depressed for an average duration of 60-70 sec, during most of which time no antidromic responses to stimuli of pretetanic intensity were recorded. There was no significant interaction between stimuli to the terminals at rates of 1 or 0.5/sec.2. Potassium-free solutions at first increased, then decreased, the post-tetanic depression of excitability. Raising [K](o) threefold (15 mM) abolished the post-tetanic depression and often converted it to an exaltation of excitability.3. Polarizing currents were applied to the terminals with a second electrode. Depolarizing currents increased, while hyperpolarizing currents decreased, the post-tetanic depression of excitability.4. In solutions with 70% of the normal NaCl content replaced by sucrose, the post-tetanic depression of excitability was reversibly prolonged.5. In the presence of 7.7 x 10(-6)M digoxin or 0.42 mM ouabain there was a small reversible reduction of post-tetanic excitability.6. After exposure to solutions containing no glucose or to solutions containing 3-5 mM sodium azide the excitability of the terminals was not altered by the tetanus. After washing with the control solution, post-tetanic depression of excitability returned. Antimycin-A (1.8 x 10(-6)M) had little or no effect upon post-tetanic excitability.7. It was concluded that the post-tetanic depression of excitability reflected hyperpolarization of the terminals and that this hyperpolarization was caused by a shift of the membrane potential towards the potassium equilibrium potential because of an increase in potassium permeability.

Animals↗