Article (Scientific journals)
Sulfonylurea-sensitive potassium current evoked by sodium-loading in rat midbrain dopamine neurons.
Seutin, Vincent; Shen, K. Z.; North, R. A. et al.
1996In Neuroscience, 71 (3), p. 709-19
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Keywords :
Animals; Barium/pharmacology; Diazoxide/pharmacology; Dopamine/metabolism; Dose-Response Relationship, Drug; Male; Mesencephalon/drug effects; Potassium Channels/drug effects; Rats; Rats, Sprague-Dawley; Sodium/pharmacology; Urea/pharmacology
Abstract :
[en] In Parkinson's disease, there is evidence of impaired mitochondrial function which reduces the capacity to synthesize ATP in dopamine neurons. This would be expected to reduce the activity of the sodium pump (Na+/K+ ATPase), causing increased intracellular levels of Na+. Patch pipettes were used to introduce Na+ (40 mM in pipette solutions) into dopamine neurons in the rat midbrain slice in order to study the electrophysiological effects of increased intracellular Na+. We found that intracellular Na+ loading evoked 100-300 pA of outward current (at -60 mV) and increased whole-cell conductance; these effects developed gradually during the first 10 min after rupture of the membrane patch. Extracellular Ba2+ reduced most of the outward current evoked by Na+ loading; this Ba(2+)-sensitive current reversed direction at the expected reversal potential for K+ (EK), and was also blocked by extracellular tetraethylammonium (30 mM) and intracellular Cs+ (which replaced K+ in pipette solutions). The sulfonylurea drugs glipizide (IC50 = 4.9 nM), tolbutamide (IC50 = 23 microM) and glibenclamide (1 microM) were as effective as 300 microM Ba2+ in reducing the K+ current evoked by Na+ loading. When recording with "control" pipettes containing 15 mM Na+, diazoxide (300 microM) increased chord conductance and evoked outward current at -60 mV, which also reversed direction near EK. Effects of diazoxide were blocked by glibenclamide (1 microM) or glipizide (300 nM). Diazoxide (300 microM) and baclofen (3 microM), which also evoked K(+)-mediated outward currents recorded with control pipettes, caused little additional increases in outward currents during Na+ loading. Raising ATP concentrations to 10 mM in pipette solutions failed to significantly reduce currents evoked by diazoxide or Na+ loading, suggesting that these currents may not be mediated by ATP-sensitive K+ channels. Finally, Na+ loading using pipettes containing Cs+ in place of K+ evoked a relatively small outward current (50-150 pA at -60 mV), which developed gradually over the first 10 min after rupturing the membrane patch. This current was reduced by dihydro-ouabain (3 microM) and a low extracellular concentration of K+ (0.5 mM instead of 2.5 mM), but was not affected by Ba2+. We conclude that intracellular Na+ loading evokes a current generated by Na+/K+ ATPase in addition to sulfonylurea-sensitive K+ current. This Na(+)-dependent K+ current is unusual in its sensitivity to sulfonylureas, and could protect dopamine neurons against toxic effects of intracellular Na+ accumulation.
Disciplines :
Pharmacy, pharmacology & toxicology
Author, co-author :
Seutin, Vincent ;  Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Pharmacologie
Shen, K. Z.
North, R. A.
Johnson, S. W.
Language :
English
Title :
Sulfonylurea-sensitive potassium current evoked by sodium-loading in rat midbrain dopamine neurons.
Publication date :
1996
Journal title :
Neuroscience
ISSN :
0306-4522
eISSN :
1873-7544
Publisher :
Elsevier Science, New York, United States - New York
Volume :
71
Issue :
3
Pages :
709-19
Peer reviewed :
Peer Reviewed verified by ORBi
Available on ORBi :
since 28 April 2010

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