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J D Cooke

Publications and source records attributed to J D Cooke.

45 records · Page 3Linked to original sources
PubMed1973

Cumulative and persistent effects of nerve terminal depolarization on transmitter release.

1. Following focal depolarization of rat motor nerve terminals there could often be observed an ;after-discharge' of m.e.p.p.s with transient frequencies of up to 1000/sec. This after-discharge was graded with intensity and duration of the previous depolarization.2. Following pulses which were relatively short (about 1 sec) and not too large (< -100 mV local extracellular potential field) the logarithm of m.e.p.p. frequency fell exponentially. With larger or longer pulses there was a tail to the after-discharge which could persist for several minutes.3. M.e.p.p. frequency during an after-discharge was not inhibited appreciably by nerve terminal hyperpolarization, raised [Ca] (8 mM) or lowered pH.4. Measured as a multiplication of spontaneous m.e.p.p. frequency after-discharge was depressed in solution containing no Ca(2+) and added 1 mM-MgEDTA but equal in 0.125 mM-Ca(2+) or 2 mM-Sr(2+) to that in 2 mM-Ca(2+) or 8 mM-Ca(2+).5. During an after-discharge the multiplication of m.e.p.p. frequency by focal nerve terminal depolarization or raised K(+) was reduced. This phenomenon was termed ;uncoupling'.6. It was concluded that the after-discharge is not caused by a persistent rise of K(+) concentration in the synaptic cleft, nor by a maintained nerve terminal depolarization.7. In preparations depolarized by raised K(+) m.e.p.p. frequency during a relatively small focal depolarizing pulse rose continuously, after an initial rapid rise, and after the pulse there was a tail of increased m.e.p.p. frequency. The magnitude of the rise during the pulse and the tail after it were similar on, a logarithmic basis; during both processes the logarithm of m.e.p.p. frequency usually followed (approximately) an exponential time course.8. The relative magnitude of the slow effect of depolarization, as compared with the fast effect, was increased by lowering [Ca] or increasing [Mg], and the slow effect of depolarization in contrast to the fast effect was found to exist in the presence of Ca reduced to about 10(-7)M, but only during pulses. At this [Ca] there was no rapid response to depolarization. At [Ca] about 10(-10)M, there was no response at all of m.e.p.p. frequency to nerve terminal depolarization.9. The results are discussed, and compared with similar data referring to ;facilitation' and ;post-tetanic potentiation'. It is concluded that these and the slow effect of depolarization represent the same phenomenon, a response of the transmitter release system which can be distinguished from the fast response in terms of ionic requirement as well as time course.

Animals↗
PubMed1973

The specific effect of potassium on transmitter release by motor nerve terminals and its inhibition by calcium.

1. There exist two distinct effects of potassium on the transmitter release system, one which develops rapidly and another which becomes maximal much more slowly. The fast effect is inhibited by raised Ca(2+), which does not inhibit transmitter release evoked by depolarizing pulses. Thus the fast effect is not secondary to nerve terminal depolarization.2. The fast effect of K(+) was found to consist in an increase in the slope of the linear relation between log m.e.p.p. frequency and nerve terminal depolarization. This effect is complete within a few seconds, is inhibited by raised Ca(2+), and is not produced by prolonged focal or electrotonic depolarization, which instead tends to reduce the slope of log m.e.p.p. frequency vs. depolarization.3. A slope change effect like that of K(+) was not found with ouabain or ethanol, nor did these agents depress the slope change effect of K(+). The specific action of K(+) was not exerted on release evoked in the absence of Ca(2+) by ethanol, chloral hydrate, or raised osmotic pressure.4. It is suggested that the specific action of K(+) is to increase the lability of nerve terminal Ca permeability with respect to depolarization of the nerve terminal membrane, while the slow effect of K(+) simply reflects nerve terminal depolarization, slow to become maximal because of diffusion barriers limiting access of raised K(+) to the Ranvier nodes of motor axons.

Animals↗
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↗
PubMedDate not supplied

Control of simple arm movements in elderly humans.

Eight elderly subjects (aged 68-95 years) and 6 young adults (aged 21-24 years) performed elbow flexion and extension movements in a visual step-tracking paradigm. Movement amplitudes ranging from 10 degrees-80 degrees were made under two instructions: "move at own speed" and "move fast and accurate." In a second experiment, 5 elderly subjects practiced 30 degrees movements for a total of 180 flexion and 180 extension movements under the instruction to increase movement speed, while maintaining accuracy, during practice. Movement trajectories became more variable as both movement amplitude and speed increased. Trajectory variability was greater in the elderly subjects for both the acceleratory and deceleratory phases of movements. This was due primarily to a greater rate of increase in trajectory variability during the acceleration phase in the elderly. With practice, elderly subjects could substantially reduce trajectory variability with little change in movement speed. The agonist burst initiating movements was qualitatively normal in the elderly subjects. However, there was considerable tonic cocontraction of agonist and antagonist muscles prior to and during movement. Phasic antagonist EMG activity was obviously abnormal in many elderly subjects. There was often no clear antagonist burst associated with deceleration of the movements or, if present, it was timed inappropriately early. With practice, combined agonist-antagonist EMG variability decreased. A clear antagonist burst also developed during practice in most elderly subjects, but its inappropriate timing remained in all but one subject. The results show that movement trajectories are less accurately controlled in the elderly.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMedDate not supplied

Kinematics of arm movements in elderly humans.

Changes in the kinematics of arm movements with age were studied. "Young" (aged 21-23) and "elderly" (aged 68-95) subjects performed a visually guided, step tracking task. Each subject performed movements of eight different amplitudes (10-80 deg) at two volitionally determined speeds ("own speed," "fast and accurate"). Movement durations and maximum velocities were similar for both groups and increased with movement amplitude under all conditions. The young subjects made movements in which approximately the same length of time was spent in accelerating as in decelerating the movement. In contrast, movements by the elderly subjects were temporally asymmetrical, the deceleration phase being longer than the acceleration phase. The ratio of maximum to average velocities (Vm/Vav) was markedly different between the young and elderly subjects, particularly in the smaller amplitude movements (less than 40 deg). Values of this parameter ranged from 1.5 to 6 in the elderly subjects. Movements made by the elderly subjects were more variable than those of the young subjects, particularly so at smaller amplitudes. Variability was most apparent in the deceleratory phase of movement where the elderly subjects often showed hypermetria. Some elderly subjects also showed movement decomposition, the movements being made as a series of discrete submovements. Thus, the elderly subjects displayed some of the characteristics classically described as arising from cerebellar dysfunction.

Adult↗