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D M Quastel

Publications and source records attributed to D M Quastel.

47 records · Page 3Linked to original sources
PubMed1973

The role of calcium in depolarization-secretion coupling at the motor nerve terminal.

1. The relation between m.e.p.p. frequency (F) and [Ca] was studied at the mouse neuromuscular junction, at varied concentrations of K(+) and at nerve terminals depolarized by focal depolarization.2. Under all conditions the relation between log F and log [Ca] was sigmoid, with a maximum slope that increased with depolarization or raised [K(+)]. In addition, depolarization or raised K(+) caused a progressive shift of the sigmoid curve upward and to the left (to reduced log [Ca]) and increased the range over which log F could be altered by [Ca].3. Reduction of osmotic pressure changed the relation between log F and log [Ca] in the same way as increase of depolarization, while increase of osmotic pressure did the opposite.4. Raised [Mg] acted in two ways: (a) to shift the curve of log F vs. log [Ca] to the right and (b) to reduce maximum Delta log F/Delta log [Ca] without altering the range of log F sensitive to [Ca].5. The relation between log quantal content of e.p.p.s and log [Ca] was similar to that between log m.e.p.p. frequency and log [Ca].6. Individual nerve terminals varied in both Ca-dependent and Ca-independent fractions of log F; a large Ca-independent portion appears to be associated with a low Ca-dependent portion and vice versa. With large prolonged depolarization the Ca-independent portion was increased, apparently at the expense of the Ca-dependent portion.7. The results of all experiments were summarized in terms of parameters found by fitting the observed log release -log [Ca] curves to two theoretical equations, each derived on the basis of a model: (a) all-or-nothing activation of release probability by Ca-complex(es) and (b) graded activation of release probability by Ca complex(es).8. On the basis of the all-or-nothing model, from which follows alinear relation between F and amounts of Ca complex(es), the number of Ca(2+) atoms that ;cooperate' to mediate release appeared to increase progressively with presynaptic depolarization, to a value of 4 or more with a presynaptic action potential.9. On the basis of the graded activation model, which predicts an exponential relation between F and amount of Ca complex, the number of Ca(2+) atoms that combine with Ca receptor appears to be independent of presynaptic depolarization.10. Various models which could account for the data are discussed. It was concluded that all the data are consistent with a model in which:(i) quantal release probability is continuously graded with the amount of a simple Ca complex (CaX) inside the nerve terminal.(ii) Ca entry is governed by presynaptic membrane potential (increasing exponentially with depolarization) and by the amount of a Ca complex (Ca(2)Y) on or in the membrane.(iii) Mg(2+) competes with Ca(2+) at both receptors, X and Y.(iv) The internal Ca receptor X is also increased by presynaptic depolarization.

Action Potentials↗
PubMed1971

Calcium: is it required for transmitter secretion?

Ethanol multiplies miniature end-plate potential frequency independently of calcium ion concentrations and also multiplies calcium-dependent depolarization-evoked quantal release, to the same extent. This result implies a final common pathway, requiring little or no calcium, for both kinds of transmitter secretion. Chlorpromazine and hypertonicity act similarly to ethanol, but also depress depolarization-secretion coupling.

Animals↗
PubMed1966

Competition between sodium and calcium ions in transmitter release at mammalian neuromuscular junctions.

1. Frequencies of miniature end-plate potentials (m.e.p.p.s) were recorded at neuromuscular junctions in rat diaphragm-phrenic nerve preparations in vitro.2. In the presence of raised [K] (15-20 mM) lowering [Na] caused a rapid increase in m.e.p.p. frequency whether [Ca] was low or normal. Raising [Na] towards the normal concentration (162 mM) caused a slow fall in frequency and raising [Ca] in the range 0.32-2 mM caused a slow increase in frequency. These effects were less in the normal [K] (5 mM).3. Mean m.e.p.p. frequencies were determined for solutions containing 15 mM-K and combinations of [Ca] and [Na]. M.e.p.p. frequency varied inversely with [Na] when [Ca] was constant. In each of the three Na concentrations used (162, 113 and 65 mM) raising [Ca] in the range 0.32-2 mM increased m.e.p.p. frequency but when raised above 2-3 mM, Ca depressed frequency.4. A model was proposed in which Ca affected transmitter release by changing the concentration in the presynaptic membrane of a complex CaX to which the rate of transmitter release was directly proportional. Higher concentrations of Ca depressed transmitter release by inactivating CaX. Sodium ions competitively depressed release either by competing with calcium ions for association with X or by reducing the affinity of X for Ca.5. When [Na] was lowered in solutions containing raised [Mg] and [Ca], the increase of mean m.e.p.p. frequency was greater than that observed in raised [Ca] and normal [Mg] and was of the same order as the increases seen in low [Ca]. The result was interpreted to indicate either that Na and Mg do not compete with Ca at the same site or that Mg affects the affinity of X for Ca and Na.6. The effect of lowering [Na] on m.e.p.p. frequency was a specific effect of Na ions. When LiCl was substituted for NaCl, the increase of m.e.p.p. frequency persisted. Changes in [Cl] had no effect on m.e.p.p. frequency.7. There was a linear relation between the mean logarithm of m.e.p.p. frequencies and [K], the slope of the relation increasing as [Na] was lowered. Conversely, lowering [Na] caused a greater increase in m.e.p.p. frequency as [K] was raised.8. The variation of m.e.p.p. frequencies in a diaphragm was roughly proportional to a second or higher power of [Na] and inversely proportion to [Ca]. It was thought that this could be due to differences in chelation of Ca which were more apparent at low Ca concentrations.9. The similarities between the effects of Na, Ca and K on m.e.p.p. frequency and the effects of these ions on Ca-influx in heart muscle led to the suggestion that transmitter release is proportional to the concentration of a negatively charged complex of a carrier X with one calcium ion (CaX) at the internal surface of the membrane and that changes in membrane potential affect transmitter release by changing the distribution or location of CaX in the membrane.

Animals↗