Effects of KRN2391 on ionic currents in rabbit femoral arterial myocytes

The effects of KRN2391, an ATP‐sensitive K + channel opener (KCO) which also acts as a nitrate, on ionic membrane currents in rabbit femoral arterial myocytes were examined. Under whole‐cell clamp conditions where cells were superfused with physiological salts solution containing 5.9 m M K + , KRN2391 elicited an outward current at a holding potential of −30 mV. KRN2391‐induced current had a reversal potential of −78 mV and was abolished by glibenclamide (glib). KRN2391 was approximately 25 times more potent than nicorandil to activate an ATP‐sensitive K + current ( I KATP ). On the other hand, 10 μ M KRN2391 did not affect either voltage‐dependent Ca 2+ or delayed rectifier K + channel currents. In the inside‐out patch configuration, KRN2391 activated 47 pS K + channels in the presence of nucleotide diphosphates (NDPs) under the symmetrical 140 m M K + conditions. Glib and intracellular ATP reversibly inhibited the activity of the 47 pS K + channels. The 47 pS K + channels activated by KRN2391 are similar in their conductance and other properties to NDP‐sensitive K + channels (K NDP channels) described in other smooth muscles and the cloned channels. KRN2391 is a potent activator of the 47 pS K + channels and the activation can contribute to the KRN2391‐induced vasodilation in arterial muscles.British Journal of Pharmacology (2001) 132 , 1154–1160; doi: 10.1038/sj.bjp.0703903