Referenced in: none

Automatically associated channels: Kir6.1

Title: Effects of KRN4884, a novel K+ channel opener, on ionic currents in rabbit femoral arterial myocytes.

Authors: Katsuhiko Muraki, Akiko Sasaoka, Susumu Ohya, Minoru Watanabe, Yuji Imaizumi

Journal, date & volume: J. Pharmacol. Sci., 2003 Nov , 93, 289-98

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/14646246

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.