TY - JOUR
T1 - Sites of action of procaine at the motor end‐plate.
AU - Gage, P. W.
AU - Hamill, O. P.
AU - Wachtel, R. E.
PY - 1983/2/1
Y1 - 1983/2/1
N2 - 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. Following exposure to procaine (0.05-0.1 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. 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. 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. These results suggest that the procaine applied at high pH, where it is predominantly in unchanged form, may be diffusing to a site of action which is not directly accessible from the external surface of the membrane. The voltage-dependence of procaine action wss similar whether it was applied at pH 7.4 or 9.9. 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 me.p.c.s. was similar to that seen for biphasic m.e.p.c.s. produced by extracellular application of procaine. 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.
AB - 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. Following exposure to procaine (0.05-0.1 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. 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. 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. These results suggest that the procaine applied at high pH, where it is predominantly in unchanged form, may be diffusing to a site of action which is not directly accessible from the external surface of the membrane. The voltage-dependence of procaine action wss similar whether it was applied at pH 7.4 or 9.9. 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 me.p.c.s. was similar to that seen for biphasic m.e.p.c.s. produced by extracellular application of procaine. 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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U2 - 10.1113/jphysiol.1983.sp014524
DO - 10.1113/jphysiol.1983.sp014524
M3 - Article
C2 - 6308216
AN - SCOPUS:0020647560
SN - 0022-3751
VL - 335
SP - 123
EP - 137
JO - The Journal of Physiology
JF - The Journal of Physiology
IS - 1
ER -