High potassium-induced activation of choline-acetyltransferase in human neocortex: implications and species differences.
The role of electrical and potassium (K(+))-induced depolarisation on choline-acetyltransferase (ChAT) activity in human and mouse neocortical slices was studied. When [3H]-ACh release was evoked by two K(+) stimulations in human neocortex, the mean S(2)/S(1) ratio was significantly below unity. ChAT inhibitors, like bromo-acetylcholine and ocadaic acid, raised this ratio by 79 and 63%, respectively, suggesting that the diminished S(2)/S(1) value in the absence of ChAT inhibitors reflected an increased ChAT activity at S(2) following K(+) depolarisation at S(1). When stimulated electrically, however, the S(2)/S(1) ratio in human neocortex was near unity and ocadaic acid remained without effect. In parallel experiments on mouse neocortical slices, the S(2)/S(1) ratio was near unity in both electrically or K(+)-evoked [3H]-ACh release and was not altered by ChAT inhibition. ChAT activity following K(+) depolarisation was also determined directly. ChAT activation in human neocortical slices was highest at 10 and 20mM K(+). ChAT activity in mouse neocortical tissue was not altered by K(+) depolarisation. These results suggest that in human, but not in mouse, neocortex ChAT activity may be increased due to ongoing K(+) depolarisation. This increase of ChAT activity supports a cholinergic degeneration hypothesis which has been entitled "autocannibalism" by Wurtman [TINS 15 (1992) 177].
Sigle
J-P
JP
Sektion Klinische Neuropharmakologie der Neurologischen Universitätsklinik, Neurozentrum, Breisacher Str. 64, D-79106 Freiburg, Germany.
Zander
J
J
Ehret
A
A
Honegger
J
J
Jackisch
R
R
Feuerstein
T J
TJ
D000109:Acetylcholine / Q000378:metabolism / Q000494:pharmacology; D000293:Adolescent; D000328:Adult; D000818:Animals; D002648:Child; D002795:Choline O-Acetyltransferase / Q000378:metabolism*; D018678:Cholinergic Agents / Q000494:pharmacology; D002800:Cholinesterase Inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation / Q000379:methods; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006426:Hemicholinium 3 / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D051379:Mice; D008808:Mice, Inbred CBA; D008875:Middle Aged; D019579:Neocortex / Q000187:drug effects* / Q000201:enzymology; D019319:Okadaic Acid / Q000494:pharmacology; D010830:Physostigmine / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology*; D013045:Species Specificity; D014316:Tritium / Q000378:metabolism
D018678:Cholinergic Agents; D002800:Cholinesterase Inhibitors; D004791:Enzyme Inhibitors; D014316:Tritium; D019319:Okadaic Acid; D006426:Hemicholinium 3; D010830:Physostigmine; D002795:Choline O-Acetyltransferase; D000109:Acetylcholine; D011188:Potassium