Effects of KRN2391 on ionic currents in rabbit femoral arterial myocytes

Abstract

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.

ATP‐Sensitive K+ Channels of Vascular Smooth Muscle Cells

“…The unitary conductance of heteromeric channels with ratios of Kir6.1 to Kir6.2 of 3:1 and 2:2 is within the range reported for K NDP , and these subtypes display sensitivity to NDPs 64,65 . However, heteromeric Kir6.1‐Kir6.2 subtypes cannot account for the 47‐pS K ATP channel of femoral arterial myocytes that are inactive in the absence of nucleotides 106 . The spontaneous activity in zero ATP solutions and activation by PKC demonstrated by all heteromeric Kir6.1‐Kir6.2 channels 64,65,99 preclude their categorization as K NDP channels.…”

Effects of KRN4884, a Novel K+ Channel Opener, on Ionic Currents in Rabbit Femoral Arterial Myocytes

“…Single smooth muscle cells were enzymatically dispersed from the femoral artery of the rabbit. The procedures for cell-dispersion were similar to those previously described (7,18,19). Briefly, male New Zealand White rabbits, weighing 1.5 -2.0 kg, were anesthetized with sodium thiopental (70 mg / kg, i.v.).…”