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A study of the mechanism of quantal transmitter release at a chemical synapse

A study of the mechanism of quantal transmitter release at a chemical synapse

1968

The Journal of Physiology

1968

1968

The Journal of Physiology

V. 199, № 1, 11-35

V. 199, № 1, 11-35

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Abstract

Abstract

АННОТАЦИЯ

АННОТАЦИЯ

1. The nerve-muscle preparation of the cutaneous pectoris of the frog has been used to study quantal transmitter release.

2. When the osmotic pressure of the external solution is raised 1·5-2 fold, the frequency of miniature end-plate potentials (m.e.p.p.s) rises by 1·5-2 orders of magnitude. This effect is independent of the presence of Ca2+ ions and of the nature of the substances by which the osmotic pressure has been increased.

3. In Ca2+ free hypertonic solution the nerve impulse still invades the nerve terminals but does not alter the frequency of the m.e.p.p.s.

4. The arrival of the impulse in the terminals causes an immediate increase in the rate of quantal release, provided divalent cations are present whose passage through the axon membrane is facilitated by excitation (Ca2+, Sr2+, Ba2+).

5. Divalent cations which penetrate only slightly (Mg2+, Be2+) lower the frequency of m.e.p.p.s and suppress the end-plate potential (e.p.p.) evoked by an impulse, in the presence of Ca2+ ions. Be2+ is a more effective inhibitor than Mg2+.

6. In Ca2+ free solutions, adding Mg2+ causes an increase in the frequency of m.e.p.p.s evoked by depolarization of the nerve endings or by treatment with ethanol.

7. The trivalent cation La3+ is more effective than divalent cations are in increasing the frequency of m.e.p.p.s. The tetravalent cation Th4+ also raises the m.e.p.p. frequency.

8. The observations summarized in paragraphs 2-7 indicate that the frequency of m.e.p.p.s at a constant temperature depends only on the concentration of uni-, di- and trivalent cations inside the nerve ending. It is suggested that the internal cation concentration influences the adhesion between synaptic vesicles and the membrane of the nerve ending.

9. For a model experiment, artificial phospholipid membranes have been used to study the effect of uni-, di-, tri- and tetravalent cations on the adhesion process. At pH 7-7·4, the time required for adhesion to take place decreases with increasing cation concentration in the bath. Ca2+ ions are 100-1000 times more effective than K+ ions; La3+ and Th4+ ions are still more effective. The "adhesion time" decreases when the pH is lowered; it increases greatly with lowering of temperature.

10. The hypothesis is put forward that the mutual adhesion of artificial vesicles made of phospholipid membranes, and the adhesion between synaptic vesicles and the membrane of the nerve ending arise by a common mechanism. In both cases, the important factor is the influence of cations on the electric double layer at the membrane surface.

1. The nerve-muscle preparation of the cutaneous pectoris of the frog has been used to study quantal transmitter release.

2. When the osmotic pressure of the external solution is raised 1·5-2 fold, the frequency of miniature end-plate potentials (m.e.p.p.s) rises by 1·5-2 orders of magnitude. This effect is independent of the presence of Ca2+ ions and of the nature of the substances by which the osmotic pressure has been increased.

3. In Ca2+ free hypertonic solution the nerve impulse still invades the nerve terminals but does not alter the frequency of the m.e.p.p.s.

4. The arrival of the impulse in the terminals causes an immediate increase in the rate of quantal release, provided divalent cations are present whose passage through the axon membrane is facilitated by excitation (Ca2+, Sr2+, Ba2+).

5. Divalent cations which penetrate only slightly (Mg2+, Be2+) lower the frequency of m.e.p.p.s and suppress the end-plate potential (e.p.p.) evoked by an impulse, in the presence of Ca2+ ions. Be2+ is a more effective inhibitor than Mg2+.

6. In Ca2+ free solutions, adding Mg2+ causes an increase in the frequency of m.e.p.p.s evoked by depolarization of the nerve endings or by treatment with ethanol.

7. The trivalent cation La3+ is more effective than divalent cations are in increasing the frequency of m.e.p.p.s. The tetravalent cation Th4+ also raises the m.e.p.p. frequency.

8. The observations summarized in paragraphs 2-7 indicate that the frequency of m.e.p.p.s at a constant temperature depends only on the concentration of uni-, di- and trivalent cations inside the nerve ending. It is suggested that the internal cation concentration influences the adhesion between synaptic vesicles and the membrane of the nerve ending.

9. For a model experiment, artificial phospholipid membranes have been used to study the effect of uni-, di-, tri- and tetravalent cations on the adhesion process. At pH 7-7·4, the time required for adhesion to take place decreases with increasing cation concentration in the bath. Ca2+ ions are 100-1000 times more effective than K+ ions; La3+ and Th4+ ions are still more effective. The "adhesion time" decreases when the pH is lowered; it increases greatly with lowering of temperature.

10. The hypothesis is put forward that the mutual adhesion of artificial vesicles made of phospholipid membranes, and the adhesion between synaptic vesicles and the membrane of the nerve ending arise by a common mechanism. In both cases, the important factor is the influence of cations on the electric double layer at the membrane surface.

chaimatics

Chaimatics

Discovery of links between the biology, physics and mathematics, and founding a new area of studies focused on computations in living systems are his life achievements. Efim Liberman gave the name of “Chaimatics” to this new area of science

I

DNA is the text of a code written for molecular computers of living cells. The notion of “Text” is intrinsically opposite to a random sequence of symbols, and it can exist only inside the system of language. In this case, it is a genetic language, which is isomorphic to a natural language

II

Computations conducted in a living cell are real physical actions, and free energy and time must be spent for completing them. As all living organisms are comprised of cells, this statement is applicable to any control processes implemented in the biosphere

III

Molecular computations are limited by the microscopic scale of a cell and inevitable impact of the computations on formulation of a problem begin solved. The Chaimatics grew from the recognition of the computation reality as the quantum mechanics grew from the recognition of the measurement reality.

IV

A cell creates а quantum computing tool for solving complex problems. This tool utilizes hypersound quanta, and uses the cell cytoskeleton as the computing environment. In such a computer, a price of elementary computation converges to the physical limit, which is Planck’s constant

Chaimatic's statements are simple, but they require a change in the traditional vision, rooted in scientific practice

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Chapter I

The journey of life in science

chaimatics

хаиматика

хаиматика

Итогом жизни в науке стало установление связей между биологией, физикой, математикой и новая область исследования, посвященная вычислениям в живых системах. Ефим Либерман дал имя новой науке: «Хаиматика»

I

ДНК – это текст программы для молекулярных компьютеров клеток. «Текст» по определению не случайная последовательность знаков и может существовать только внутри языковой системы. В данном случае это генетический язык, изоморфный естественному языку

II

Вычисление в живой клетке является реальным физическим действием и требует затрат свободной энергии и времени. Поскольку все живые организмы состоят из клеток, это относится ко всему управлению, которое осуществляется в биосфере

III

Молекулярные вычисления ограничены микроскопическим объемом клетки и принципиальной возможностью влияния вычисления на условия решаемой задачи: квантовая механика возникла из осознания реальности измерения, Хаиматика - из реальности вычисления

IV

Для решения сложных задач клетка создает устройство квантового вычисления, использующего кванты гиперзвука и клеточный цитоскелет, как вычисляющую среду. Цена вычисления в таком компьютере стремится к физическому пределу – постоянной Планка

Утверждения Хаиматики просты, но они требуют изменения традиционных представлений, принятых в научной практике

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Глава I

Как все начиналось

хаиматика