Molecular Pharmacology, Vol 12, 1082-1090, Copyright © 1976 by the American Society for Pharmacology and Experimental Therapeutics

Activation of High-Affinity Choline Uptake in Vitro by Depolarizing Agents

¹ Departments of Pharmacology and Experimental Therapeutics and of Psychiatry and the Behavioral Sciences, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205

Incubation of rat brain hippocampal synaptosomes under depolarizing conditions, i.e., with veratridine or high concentrations of potassium, resulted in activation of sodium-dependent, high-affinity choline uptake. The depolarizing incubation did not affect the sodium-dependent uptake of octopamine, serotonin, or -aminobutyric acid. Omission of calcium during the incubation period with depolarizing agents, or addition of a calcium antagonist, Bay a 1040, prevented the increase in choline uptake. Omission of magnesium was without effect. Partial replacement of sodium with either lithium or sucrose, treatments which also enhance calcium influx into synaptosomes, resulted in an increase in choline uptake. These data in vitro suggest that calcium influx is an important feature of the activation of sodium-dependent, high-affinity choline uptake in vivo. Furthermore, the characteristics of the activation in vitro are similar to those observed in vivo; thus the system in vitro should be useful in exploring further the mechanisms involved in the activation of sodium-dependent, high-affinity choline uptake caused by neuronal activity in vivo.

Note:
ACKNOWLEDGMENTS The authors thank Mr. Robert DeHaven and Mrs. Naomi Taylor for their expert technical assistance, and Mrs. Nancy Hiatt and Victoria Rhodes for typing the manuscript. They also thank Dr. Samir Atweh for his helpful discussion and suggestions, and Dr. David Triggle for his generous gift of Bay a 1040.

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