Differential effects of potassium channel blockers on extracellular concentrations of dopamine and 5-HT in the striatum of conscious rats.
1. The selective Ca(2+)-activated K+ channel blocker apamin increased extracellular 5-hydroxytryptamine (5-HT) concentrations in the striatum when administered through the microdialysis probe at doses of 0.1 mM and 1 mM. Extracellular dopamine concentrations increased only at the highest dose administered (1 mM). 2. Mast cell degranulating peptide (MCDP), which blocks the dendrotoxin sensitive delayed rectifier (DR) current, increased extracellular concentrations of dopamine at dose of 10 microM-100 microM but had no effect on 5-HT. 3. The non selective K+ channel blocker tetraethylammonium (TEA) induced a dose-dependent (1 mM-10 mM) increase in extracellular dopamine concentrations and an increase in 5-HT which showed little or no dose-dependency. 4. 4-Aminopyridine (4-AP), a blocker with some similar characteristics to MCDP, increased extracellular dopamine concentrations at doses of 10 microM-1 mM, but had no effect on 5-HT. 5. These findings suggest that dopamine release may be modulated by DR-like current and/or A-current K+ channels. However, in view of the similar effects of MCDP and 4-AP at the concentrations used it is more likely that the dendrotoxin-sensitive DR-like current is involved. In contrast, 5-HT release appears to be modulated by Ca(2+)-activated K+ channels.
Dawson
L A
LA
Department of Neurophamacology, Wyeth Research (UK), Taplow, Maidenhead, Berkshire.
Routledge
C
C
D015761:4-Aminopyridine / Q000494:pharmacology; D000818:Animals; D001030:Apamin / Q000494:pharmacology; D001514:Bee Venoms / Q000494:pharmacology; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D008297:Male; D010455:Peptides / Q000494:pharmacology; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000378:metabolism*; D019789:Tetraethylammonium; D013757:Tetraethylammonium Compounds / Q000494:pharmacology
D001514:Bee Venoms; D010455:Peptides; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D013757:Tetraethylammonium Compounds; D001030:Apamin; C008331:mast cell degranulating peptide; D012701:Serotonin; D019789:Tetraethylammonium; D015761:4-Aminopyridine; D004298:Dopamine