Specific blockade of slowly activating IsK channels by chromanols—impact on the role of IsK channels in epithelia
H Suessbrich, M Bleich, D Ecke, M Rizzo, S Waldegger… - FEBS letters, 1996 - Elsevier
FEBS letters, 1996•Elsevier
Chromanols, which were recently shown to inhibit cAMP-mediated Cl− secretion in colon
crypts via a blockade of a cAMP-activated K+ conductance, were analyzed for their effects
on distinct cloned K+ channels expressed in Xenopus oocytes. The lead chromanol 293B
specifically inhibited IsK channels with an IC50 of 7 μmol/l without affecting the delayed
rectifier Kv1. 1 or the inward rectifier Kir2. 1. Moreover, several other chromanols displayed
the same rank order of potency for IsK inhibition as demonstrated in colon crypts. Finally, we …
crypts via a blockade of a cAMP-activated K+ conductance, were analyzed for their effects
on distinct cloned K+ channels expressed in Xenopus oocytes. The lead chromanol 293B
specifically inhibited IsK channels with an IC50 of 7 μmol/l without affecting the delayed
rectifier Kv1. 1 or the inward rectifier Kir2. 1. Moreover, several other chromanols displayed
the same rank order of potency for IsK inhibition as demonstrated in colon crypts. Finally, we …
Chromanols, which were recently shown to inhibit cAMP-mediated Cl− secretion in colon crypts via a blockade of a cAMP-activated K+ conductance, were analyzed for their effects on distinct cloned K+ channels expressed in Xenopus oocytes. The lead chromanol 293B specifically inhibited IsK channels with an IC50 of 7 μmol/l without affecting the delayed rectifier Kv1.1 or the inward rectifier Kir2.1. Moreover, several other chromanols displayed the same rank order of potency for IsK inhibition as demonstrated in colon crypts. Finally, we tested the effects of the previously described IsK blocker azimilide on cAMP mediated Cl− secretion in rat colon crypts. Similar to 293B azimilide inhibited the forskolin induced Cl− secretion. These data suggest that IsK protein induced K+ conductances are the targets for the chromanol 293B and its analogues, and azimilide.
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