The effect of racemic ketamine on the large conductance Ca(+2)-activated potassium (BK) channels in GH3 cells.
Recently, inhalation anesthetics have been reported to block BK channels in adrenal chromaffin cells. To determine if BK block was characteristic only of inhalation anesthetics or was also a property of other general anesthetics we examined the effects of ketamine, an intravenous general anesthetic which is structurally different than inhalation anesthetics. Cell-attached and excised patch single channel and standard whole cell recording techniques were used to examine the effect of racemic ketamine on the BK channel activity in GH3 cells. When solutions containing 150 mM KCl are used in both the pipette and bath, the BK channels are characterized as a voltage-dependent channel with a unit conductance of 150-300 pS. Racemic ketamine (at clinically relevant concentrations; 2-500 microM) selectively blocked BK channels in a dose-dependent, reversible manner as evidenced by decreases in NPo (number of channels x open probability). This decrease was due to both a decrease in mean open time and an increase in the mean closed time but without a decrease in single-channel current amplitude. Ketamine shifts the Po vs voltage curve to higher potentials without a change in the slope of the voltage dependence. Ketamine also shifts the Po vs [Ca+2] relationship to higher Ca+2 concentrations. The IC50 for the single-channel block by ketamine is 20.3 +/- 15.9 microM. In an effort to confirm that the effect of ketamine was predominantly due to a block of the BK channels, standard whole cell techniques were utilized.(ABSTRACT TRUNCATED AT 250 WORDS)
Denson
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Department of Anesthesiology, Emory University School of Medicine, Atlanta, GA 30322.
Duchatelle
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Eaton
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D000704:Analysis of Variance; D000818:Animals; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D002460:Cell Line; D018999:Charybdotoxin; D004594:Electrophysiology / Q000379:methods; D007536:Isomerism; D007649:Ketamine / Q000494:pharmacology*; D008564:Membrane Potentials / Q000187:drug effects; D010911:Pituitary Neoplasms; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D012604:Scorpion Venoms / Q000494:pharmacology; D013997:Time Factors; D014407:Tumor Cells, Cultured
D026902:Potassium Channel Blockers; D015221:Potassium Channels; D012604:Scorpion Venoms; D018999:Charybdotoxin; D007649:Ketamine; D002118:Calcium