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EFFECT OF POTASSIUM DEPOLARIZATION AND PREGANGLIONIC NERVE STIMULATION ON THE METABOLISM OF [ 3 H]‐CHOLINE IN RAT ISOLATED SYMPATHETIC GANGLIA
Author(s) -
HIGGINS A.J.,
NEAL M.J.
Publication year - 1982
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1982.tb09335.x
Subject(s) - depolarization , stimulation , choline , potassium , sympathetic nervous system , neuroscience , chemistry , biophysics , superior cervical ganglion , endocrinology , medicine , biology , biochemistry , organic chemistry , blood pressure
1 The effects of potassium depolarization and preganglionic nerve stimulation on the metabolism of [ 3 H]‐choline in the isolated superior sympathetic ganglion of the rat have been studied. 2 When unstimulated (resting) ganglia were incubated for 10 min with a low concentration (0.1 μ m ) of [ 3 H]‐choline (high affinity uptake), approximately 75% of the accumulated radioactivity was present as [ 3 H]‐phosphorylcholine, 11% was [ 3 H]‐acetylcholine ([ 3 H]‐ACh) and the remainder was unchanged [ 3 H]‐choline. 3 Depolarization of the ganglia with K (46 m m ) before their incubation with [ 3 H]‐choline, increased [ 3 H]‐choline uptake by 70% and increased [ 3 H]‐ACh synthesis by more than 700%, so that [ 3 H]‐ACh represented almost 50% of the total radioactivity recovered. In contrast, the proportion of [ 3 H]‐phosphorylcholine fell to 36% of the total radioactivity recovered. 4 The striking effect of K‐depolarization on [ 3 H]‐ACh synthesis in ganglia occurred at a concentration of 30 m m or above, and the maximum effect was seen at 45–50 m m . 5 Chronic denervation of the ganglia abolished all the effects of high‐K on [ 3 H]‐choline metabolism. In resting ganglia, [ 3 H]‐ACh formation was reduced by over 80% but [ 3 H]‐phosphorylcholine synthesis and the level of unchanged [ 3 H]‐Ch were not affected by denervation. 6 Exposure of the ganglia to low‐Na or hemicholinium‐3 (HC‐3) greatly reduced [ 3 H]‐ACh synthesis in control resting ganglia and almost abolished the effects of high‐K on [ 3 H]‐ACh synthesis. 7 Prevention of transmitter release with high‐Mg or low‐Ca medium also prevented K‐depolarization from stimulating [ 3 H]‐ACh synthesis. 8 Preganglionic nerve stimulation had an effect on [ 3 H]‐choline metabolism similar to that of K‐depolarization. Thus, at all the frequencies studied (1–30 Hz), [ 3 H]‐ACh synthesis was greatly increased and [ 3 H]‐phosphorylcholine was reduced, the maximum effects occurring at 3 Hz. 9 When ganglia were incubated with a high concentration (100 μ m ) of [ 3 H]‐choline (low affinity uptake), a different pattern of metabolism was observed. Most of the radioactivity in resting ganglia was present as unchanged [ 3 H]‐choline (70%) with [ 3 H]‐phosphorylcholine and [ 3 H]‐ACh representing 23% and 6% of the total radioactivity respectively. K‐depolarization decreased [ 3 H]‐choline uptake but increased the proportions of [ 3 H]‐phosphorylcholine and [ 3 H]‐ACh to 32% and 24% of the total radioactivity respectively. 10 It is concluded that in unstimulated (resting) rat sympathetic ganglia most of the [ 3 H]‐choline transport and metabolism occurs in postsynaptic structures. However, depolarization of the presynaptic nerve terminals appears to trigger a sodium‐dependent, HC‐3 sensitive, high‐affinity uptake process, and causes a dramatic increase in presynaptic [ 3 H]‐ACh synthesis together with a fall in postsynaptic [ 3 H]‐phosphorylcholine synthesis. These changes in choline metabolism cannot be due to the depolarization of the nerve terminals per se , because they were abolished by high‐Mg or low‐Ca, i.e. when transmitter release was prevented. Thus, the increase in ACh synthesis may be triggered by a fall in the intraterminal concentration of ACh or by the changes in Ca flux induced by depolarization. Our experiments do not provide evidence on these possible mechanisms.