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 mM 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 microM 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 mM 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.
Department of Molecular and Cellular Pharmacology, Faculty of Pharmaceutical Sciences, Nagoya City University, Nagoya 467-8603, Japan.
K
K
Muraki
A
A
Sasaoka
M
M
Watanabe
Y
Y
Imaizumi
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000502:physiology*; D000818:Animals; D005263:Femoral Artery / Q000187:drug effects* / Q000502:physiology; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D020108:Nicorandil / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects* / Q000502:physiology; D011725:Pyridines / Q000494:pharmacology*; D011817:Rabbits; D014530:Uridine Diphosphate / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology*
D015221:Potassium Channels; D011725:Pyridines; D014665:Vasodilator Agents; C070492:N-cyano-N'-(2-nitroxyethyl)-3-pyridinecarboximidamide methanesulfonate; D020108:Nicorandil; D014530:Uridine Diphosphate; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate