RT Journal Article
SR Electronic
T1 Kinetic Analysis of End Plate Currents Altered by Atropine and Scopolamine
JF Molecular Pharmacology
JO Mol Pharmacol
FD American Society for Pharmacology and Experimental Therapeutics
SP 514
OP 529
VO 14
IS 3
A1 M. ADLER
A1 E. X. ALBUQUERQUE
A1 F. J. LEBEDA
YR 1978
UL http://molpharm.aspetjournals.org/content/14/3/514.abstract
AB The decay phase of end plate currents in voltage-clamped frog sartorius muscle follows a single exponential function whose rate varies with membrane potential. Atropine increased the end plate current decay rate and reduced its voltage sensitivity, but did not alter its exponential nature. Scopolamine transformed the end plate current decay into a biphasic waveform consisting of a rapid initial current, followed by a slow terminal current. Two kinetic models were examined for their ability to simulate these drug-induced alterations of the end plate current. The models were formulated on the assumption that the drug molecules bind to the activated transmitter-receptor complex and induce sequential conversion of the end plate channel from a transient state of high conductance to a prolonged state of low or zero conductance. Drug binding was irreversible according to model I, and the complex of drug with the end plate channel was partially conducting. In model II the binding step was made reversible, and the resulting drug-channel complex was considered to be nonconducting. The predictions from these kinetic models were compared with data from voltage-clamped end plates. The theoretical end plate currents from model II agreed closely with experimental values, while those from model I were in conflict with the data. ACKNOWLEDGMENTS The authors thank Ms. Mabel Alice Zelle for technical assistance, and Mrs. Margaret Shimkaveg for help in preparation of the manuscript.