Relationships between choline uptake, acetylcholine synthesis and acetylcholine release in isolated rat atria.
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.
D000109:Acetylcholine / Q000096:biosynthesis*; D000818:Animals; D002118:Calcium / Q000494:pharmacology; D002794:Choline / Q000378:metabolism*; D006325:Heart Atria / Q000378:metabolism; D008297:Male; D008433:Mathematics; D009206:Myocardium / Q000378:metabolism*; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012965:Sodium Chloride / Q000494:pharmacology
D012965:Sodium Chloride; D002794:Choline; D000109:Acetylcholine; D011188:Potassium; D002118:Calcium