期刊名称:Proceedings of the National Academy of Sciences
印刷版ISSN:0027-8424
电子版ISSN:1091-6490
出版年度:1979
卷号:76
期号:1
页码:531-535
DOI:10.1073/pnas.76.1.531
语种:English
出版社:The National Academy of Sciences of the United States of America
摘要:Tetraethylammonium (Et4N+) ions depressed the amplitude and accelerated the decay rate of spontaneously occurring and nerve-evoked endplate currents (EPCs) in frog sartorius muscle. The relationship between peak EPC amplitude and membrane potential became nonlinear in the presence of 100 {micro}M Et4N+, and with drug concentrations of 250 {micro}M or greater the current-voltage relationship exhibited negative conductance in the hyperpolarized region. Et4N+ modified the exponential dependence of the EPC decay on membrane potential such that the decays between -150 and -50 mV were abbreviated and voltage independent but remained near control levels at more positive membrane potentials. The minimal effective concentration of Et4N+ for altering the EPC time course was 10, and maximal effects were attained with 100 {micro}M. Little additional shortening in the EPC decay phase was detected on raising the drug concentration to 1000 {micro}M. Acetylcholine noise analysis revealed a voltage-dependent reduction in the mean channel open time, which was comparable in magnitude to the shortening in the EPC decay, and a depression of single-channel conductance. In concomitant biochemical studies, Et4N+ was found to inhibit the binding of both [3H]acetylcholine and [3H]perhydrohistrionicotoxin to receptor-rich membranes from the electric organ of Torpedo ocellata with Ki values of 200 {micro}M and 280 {micro}M, respectively. These results suggest that Et4N+ interacts with both the acetylcholine receptor and its associated ionic channel. The voltage-dependent actions of Et4N+ are attributed to blockade of the ionic channel in closed as well as open conformation.