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Abstract. Effects of KRN4884 (5-amino-N-[2-(2-chlorophenyl)ethyl]-N'-cyano-3-pyridinecarboxamidine), a novel K + channel opener, on ionic currents were examined in rabbit femoral arterial myocytes (RFAMs). Under whole-cell clamp conditions where cells were superfused with 5.9 mM K + bathing solution, KRN4884 elicited an outward current at -30 mV. KRN4884-induced current had a reversal potential of -78 mV and was abolished by application of glibenclamide (glib). KRN4884 was approximately 43 times more potent than levcromakalim in activating an ATP-sensitive K + current (I K-ATP ). On the other hand, KRN4884 affected neither voltage-dependent Ca 2+ nor delayed rectifier K + channel currents. In the inside-out patch clamp configuration where cells were superfused with the symmetrical 140 mM K + solution, KRN4884 activated 47 pS K + channels in the presence of adenosine diphosphate. Similar 47 pS K + channels, which were reversibly inhibited by glib, were recorded under outside-out patch conditions. Using RT-PCR analysis, we found that inward rectifier K channel 6.1 (Kir6.1) and sulfonylurea 2B (SUR2B) transcripts were predominantly expressed in rabbit femoral artery. These results indicate that KRN4884 potently activates I K-ATP in RFAMs. The KRN4884-sensitive 47 pS K + channel activity underlying I K-ATP is a vascular type K ATP channel consisting of Kir6.1 and SUR2B and has similar characteristics to those of ATP-sensitive K + channels activated by K + channel openers in other types of smooth muscles.

1 The e ects 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. 2 Under whole-cell clamp conditions where cells were superfused with physiological salts solution containing 5.9 mM K + , KRN2391 elicited an outward current at a holding potential of 730 mV. KRN2391-induced current had a reversal potential of 778 mV and was abolished by glibenclamide (glib). KRN2391 was approximately 25 times more potent than nicorandil to activate an ATPsensitive K + current (I KATP ). On the other hand, 10 mM KRN2391 did not a ect either voltagedependent Ca 2+ or delayed recti®er K + channel currents. 3 In the inside-out patch con®guration, KRN2391 activated 47 pS K + channels in the presence of nucleotide diphosphates (NDPs) under the symmetrical 140 mM K + conditions. Glib and intracellular ATP reversibly inhibited the activity of the 47 pS K + channels. 4 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.

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