Postsynaptic Effects of Some Central Stimulants at the Neuromuscular Junction

Gage, Peter W.; Sah, Pankaj

doi:10.1111/j.1476-5381.1982.tb09166.x

Cited by 6 publications

(4 citation statements)

References 14 publications

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“…Similar data could not be collected at pH 9-9 because the effects of procaine increased progressively with time, probably indicating that the procaine concentration at its site of action had not reached a steady-state value (Gage et al 1983). The blocking model above predicts that rf + r. should increase linearly with procaine concentration, since rf + r. fc + a + b (for ctb 4 (ac+b+fc)2) (Gage & Sah, 1982;Adams, 1976). Assuming that a and b are independent of drug concentration, a plot of rf + r8 versus c should have a slope and intercept (a + b).…”

Section: Methodsmentioning

confidence: 99%

“…However, the effects of some drugs which appear at first to be channel blockers have been found, upon closer examination, to be inconsistent with this sequential model. Hexafluorodiethyl ether produces biphasic m.e.p.c.s at the toad end-plate, but at lower temperatures the slower phase decays faster than m.e.p.c.s recorded in the absence of the drug (Gage & Sah, 1982). Barbiturates may be channel blockers at the end-plate (Adams, 1976), but do not act in a similar fashion in Aplysia.…”

Section: Introductionmentioning

confidence: 91%

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Some effects of procaine at the toad end‐plate are not consistent with a simple channel‐blocking model.

Gage¹,

Wachtel²

1984

The Journal of Physiology

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SUMMARY1. Miniature end-plate currents (m.e.p.c.s) were recorded extracellularly from toad sartorius muscle fibres exposed to solutions containing procaine at pH 5 4, 7-4 and 9.9.2. The decay phase of m.e.p.c.s was analysed to determine whether the effects of procaine were consistent with a sequential channel-blocking model.3. Averaged m.e.p.c.s measured in the presence ofprocaine were biphasic, decaying as the sum of two exponential components. However, about 10-15 % of m.e.p.c.s decayed as single exponentials and were not biphasic.4. At pH 9-9 the relative amplitudes of the fast and slow phases were generally consistent with the decay time constants, according to the predictions of the blocking model. Such a correlation was not found at pH 5-4 or 7-4. In addition, the rate of decay of m.e.p.c.s at pH 5-4 did not increase as predicted with procaine concentration.5. These results demonstrate that the sequential blocking model is unable to account for all of the effects of procaine on m.e.p.c. decay. In addition, the finding that some m.e.p.c.s are single exponential, while most are biphasic, suggests a heterogeneity of receptor-channel complexes.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 91%

Some effects of procaine at the toad end‐plate are not consistent with a simple channel‐blocking model.

Gage¹,

Wachtel²

1984

The Journal of Physiology

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“…Rate constants derived from the blocking model (Adams, 1977) were calculated according to the equations (Gage & Sah, 1982):…”

Section: Methodsmentioning

confidence: 99%

Sites of action of procaine at the motor end‐plate.

Gage¹,

Hamill²,

Wachtel³

1983

The Journal of Physiology

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SUMMARY1. The effects of procaine at pH 7-4 and 9 9 were studied by examining the decay phase of spontaneous miniature end-plate currents (m.e.p.c.s) recorded from toad sartorius muscle fibres.2. Following exposure to procaine (005-01 mM) at pH 7 4, the decay of m.e.p.c.s rapidly became biphasic, and could be described as the sum of two exponential components.3. When the same concentrations of procaine were applied at pH 9 9, the development of biphasic m.e.p.c.s took much longer. Reversal of the effect upon washing out the procaine was much slower at pH 9.9 than at pH 7*4. 4. A rapid change in pH from 7-4 to 9-9 during exposure to a constant concentration of procaine quickly reduced the effect of procaine on m.e.p.c.s. The effect gradually returned after prolonged exposure to procaine at pH 9-9.5. These results suggest that procaine applied at high pH, where it is predominantly in uncharged form, may be diffusing to a site of action which is not directly accessible from the external surface of the membrane.6. The voltage-dependence of procaine action was similar whether it was applied at pH 7*4 or 9-9. 7. Intracellular injection of procaine rapidly produced biphasic m.e.p.c.s, whether the extracellular pH was 7-4 or 9-9. The effect of membrane potential on these m.e.p.c.s was similar to that seen for biphasic m.e.p.c.s produced by extracellular application of procaine.8. The results indicate that procaine can affect end-plate channels when applied to either surface of the muscle membrane, and that the voltage-dependence of procaine action does not arise from the influence of membrane field on the movement of charged procaine molecules into open channels.

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“…the receptor-channel complex rather than by physically blocking channels. Several other drugs thought to have been simple channel blockers have also been found not to act in this way (Gage & Sah, 1982;Gage et al, 1983;Neher, 1983;Gage & Wachtel, 1984).…”

Section: Introductionmentioning

confidence: 99%