TY - JOUR
T1 - Endplate channel block by guanidine derivatives
AU - Farley, Jerry M.
AU - Yeh, Jay Z.
AU - Watanabe, Shigenori
AU - Narahashi, Toshio
PY - 1981/3/1
Y1 - 1981/3/1
N2 - The effects of the n-alkyl derivatives of guanidine on the frog neuromuscular junction were studied using the two-microelectrode voltage clamp and other eleetrophysiological techniques. Methyl-, ethyl-, and propylguanidine stimulated the nerve-evoked release of transmitter. However, amyland octylguanidine had no apparent presynaptic action. All of the derivatives blocked the postsynaptic response to acetylcholine, the potency sequence being octyl- > amyl- > propyl-, methyl- > ethylguanidine. Methyl- and octylguanidine did not protect the receptor from a-bungarotoxin block, suggesting that these compounds do not bind to the receptor but probably block the ionic channel. Methyl-, ethyl-, and propylguanidine shortened inward endplate currents but prolonged outward currents. Amylguanidine prolonged both inward and outward endplate currents, and the currents became biphasic at negative membrane potentials. Octylguanidine increased the rate of decay of endplate currents at all potentials. All of the derivatives blocked inward endplate currents more markedly than outward currents, resulting in a highly nonlinear current-voltage relation. Methyl-, ethyl-, and propylguanidine reversed the voltage dependence of endplate current decay, while amyl- and octylguanidine reduced the voltage dependence of endplate current decay. Octylguanidine appears to block the ionic channel in both the open and the closed state. The block of the open channel follows pseudo-first-order kinetics with a forward rate constant of 4-6 × 107 M-1 s-1.
AB - The effects of the n-alkyl derivatives of guanidine on the frog neuromuscular junction were studied using the two-microelectrode voltage clamp and other eleetrophysiological techniques. Methyl-, ethyl-, and propylguanidine stimulated the nerve-evoked release of transmitter. However, amyland octylguanidine had no apparent presynaptic action. All of the derivatives blocked the postsynaptic response to acetylcholine, the potency sequence being octyl- > amyl- > propyl-, methyl- > ethylguanidine. Methyl- and octylguanidine did not protect the receptor from a-bungarotoxin block, suggesting that these compounds do not bind to the receptor but probably block the ionic channel. Methyl-, ethyl-, and propylguanidine shortened inward endplate currents but prolonged outward currents. Amylguanidine prolonged both inward and outward endplate currents, and the currents became biphasic at negative membrane potentials. Octylguanidine increased the rate of decay of endplate currents at all potentials. All of the derivatives blocked inward endplate currents more markedly than outward currents, resulting in a highly nonlinear current-voltage relation. Methyl-, ethyl-, and propylguanidine reversed the voltage dependence of endplate current decay, while amyl- and octylguanidine reduced the voltage dependence of endplate current decay. Octylguanidine appears to block the ionic channel in both the open and the closed state. The block of the open channel follows pseudo-first-order kinetics with a forward rate constant of 4-6 × 107 M-1 s-1.
UR - http://www.scopus.com/inward/record.url?scp=0019464589&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0019464589&partnerID=8YFLogxK
U2 - 10.1085/jgp.77.3.273
DO - 10.1085/jgp.77.3.273
M3 - Article
C2 - 6973006
AN - SCOPUS:0019464589
SN - 0022-1295
VL - 77
SP - 273
EP - 293
JO - Journal of General Physiology
JF - Journal of General Physiology
IS - 3
ER -