The slow component of the delayed rectifier potassium current in undiseased human ventricular myocytes.
OBJECTIVE
The purpose of this study was to investigate the properties of the slow component of the delayed rectifier potassium current (I(Ks)) in myocytes isolated from undiseased human left ventricles.


METHODS
The whole-cell configuration of the patch-clamp technique was applied in 58 left ventricular myocytes from 15 hearts at 37 degrees C. Nisoldipine (1 microM) was used to block inward calcium current (I(Ca)) and E-4031 (1-5 microM) was applied to inhibit the rapid component of the delayed rectifier potassium current (I(Kr)).


RESULTS
In 31 myocytes, an E-4031 insensitive, but L-735,821 and chromanol 293B sensitive, tail current was identified which was attributed to the slow component of I(K) (I(Ks)). Activation of I(Ks) was slow (tau=903+/-101 ms at 50 mV, n=14), but deactivation of the current was relatively rapid (tau=122.4+/-11.7 ms at -40 mV, n=19). The activation of I(Ks) was voltage independent but its deactivation showed clear voltage dependence. The deactivation was faster at negative voltages (about 100 ms at -50 mV) and slower at depolarized potentials (about 300 ms at 0 mV). In six cells, the reversal potential was -81.6+/-2.8 mV on an average which is close to the K(+) equilibrium potential suggesting K(+) as the main charge carrier.


CONCLUSIONS
In undiseased human ventricular myocytes, I(Ks) exhibits slow activation and fast deactivation kinetics. Therefore, in humans I(Ks) differs from that reported in guinea pig, and it best resembles I(Ks) described in dog and rabbit ventricular myocytes.
Department of Pharmacology and Pharmacotherapy, Albert Szent-Györgyi Medical University, Dóm tér 12, P.O. Box 427, H-6720, Szeged, Hungary.
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L
Virág
N
N
Iost
M
M
Opincariu
J
J
Szolnoky
J
J
Szécsi
G
G
Bogáts
P
P
Szenohradszky
A
A
Varró
J G
JG
Papp
D000328:Adult; D001569:Benzodiazepines / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002469:Cell Separation / Q000379:methods; D002839:Chromans / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D005260:Female; D006801:Humans; D015640:Ion Channel Gating / Q000187:drug effects*; D008133:Long QT Syndrome / Q000378:metabolism; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D015737:Nisoldipine / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D010880:Piperidines / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects* / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology; D013449:Sulfonamides / Q000494:pharmacology
D002121:Calcium Channel Blockers; D002839:Chromans; C115921:L 735821; D010880:Piperidines; D015221:Potassium Channels; D011725:Pyridines; D013449:Sulfonamides; C063968:E 4031; D001569:Benzodiazepines; C103474:6-cyano-4-(N-ethylsulfonyl-N-methylamino)-3-hydroxy-2,2-dimethylchromane; D005576:Colforsin; D015737:Nisoldipine