Effects of KRN4884, a novel K+ channel opener, on ionic currents in rabbit femoral arterial myocytes.
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.
Muraki
Katsuhiko
K
Department of Molecular and Cellular Pharmacology, Graduate School of Pharmaceutical Sciences, Nagoya City University, Japan. kmuraki@phar.nagoya-cu.ac.jp
Sasaoka
Akiko
A
Ohya
Susumu
S
Watanabe
Minoru
M
Imaizumi
Yuji
Y
D000818:Animals; D004305:Dose-Response Relationship, Drug; D005263:Femoral Artery / Q000187:drug effects* / Q000502:physiology; D015640:Ion Channel Gating / Q000187:drug effects*; D008297:Male; D032389:Myocytes, Smooth Muscle / Q000187:drug effects* / Q000502:physiology; D015221:Potassium Channels / Q000819:agonists / Q000502:physiology*; D011725:Pyridines / Q000494:pharmacology*; D011817:Rabbits
C096484:KRN 4884; D015221:Potassium Channels; D011725:Pyridines