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  • Title: Relationships between choline uptake, acetylcholine synthesis and acetylcholine release in isolated rat atria.
    Author: Wetzel GT, Brown JH.
    Journal: J Pharmacol Exp Ther; 1983 Aug; 226(2):343-8. PubMed ID: 6875847.
    Abstract:
    Isolated rat atria take up [3H]choline and synthesize [3H]acetylcholine (ACh). The uptake of [3H]choline has a high-affinity component with a Km of approximately 0.2 microM and a Vmax of approximately 6 fmol/min/mg wet wt. This high-affinity component of choline uptake is difficult to measure directly because it represents only a small portion of total [3H]choline uptake. However, the rate of synthesis of [3H] ACh from [3H]choline appears to reflect the activity of the high-affinity choline uptake system. Thus, [3H]ACh synthesis is most efficient at low choline concentrations and is inhibited in the presence of hemicholinium-3 and low NaCl medium. The neuronal localization of the [3H]Ach synthesized from [3H]choline is demonstrated by the finding that [3H]ACh is released from the atria by depolarization with 57 mM K+ medium. The release is Ca++ -dependent and there is a compensatory increase in the synthesis of [3H]ACh after depolarization-induced ACh release. These data suggest that [3H]choline can be specifically incorporated into a releasable pool of [3H]ACh localized in cardiac parasympathetic neurons. The synthesis of [3H]ACh is inhibited by blockade of high-affinity choline uptake and is regulated in response to neuronal activity. The application of these methods will provide a means for directly examining the physiological and pharmacological control of ACh synthesis and release from cardiac parasympathetic neurons.
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