Characterization of chromanol 293B-induced block of the delayed-rectifier K+ current in heart-derived H9c2 cells.
The effects of chromanol 293B on ion currents in rat embryonic heart-derived H9c2 cells were investigated in this study. Chromanol 293B suppressed the amplitude of delayed rectified K+ current (I(K)) in a concentration-dependent manner. The IC50 value for chromanol 293B-induced inhibition of I(K) was 8 microM. The I(K) present in these cells, the electrical properties of which resembled those for the Kv2.1-related K+ current, was sensitive to inhibition by quinidine or dendrotoxin, yet not by pandinotoxin-Kalpha, E-4031 or apamin. Chromanol 293B reduced the activation time constant of I(K) and the effective gating charge of this channel. However, little or no modification in the steady-state inactivation of I(K) in response to long-lasting conditioning pulses could be demonstrated in the presence of chromanol 293B. These results clearly demonstrate that chromanol 293B can effectively interact with the K+ channel functionally expressed in H9c2 myoblasts. The chromanol 293B-induced inhibition of these channels could primarily be attributed to open channel block.
Lo
Yi-Ching
YC
Department and Graduate Institute of Pharmacology, Kaohsiung Medical University, Kaohsiung, Taiwan.
Yang
Su-Rong
SR
Huang
Mei-Han
MH
Liu
Yen-Chin
YC
Wu
Sheng-Nan
SN
D000818:Animals; D002460:Cell Line; D002839:Chromans / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006352:Heart Ventricles / Q000166:cytology; D015640:Ion Channel Gating / Q000187:drug effects; D008564:Membrane Potentials / Q000187:drug effects; D011188:Potassium / Q000378:metabolism*; D026902:Potassium Channel Blockers / Q000494:pharmacology*; D024642:Potassium Channels, Voltage-Gated / Q000037:antagonists & inhibitors*; D051381:Rats; D013449:Sulfonamides / Q000494:pharmacology*; D016276:Ventricular Function
D002839:Chromans; D026902:Potassium Channel Blockers; D024642:Potassium Channels, Voltage-Gated; D013449:Sulfonamides; C103474:6-cyano-4-(N-ethylsulfonyl-N-methylamino)-3-hydroxy-2,2-dimethylchromane; D011188:Potassium