Drug-induced ion channel trafficking disturbance can cause cardiac arrhythmias. The subcellular level at which drugs interfere in trafficking pathways is largely unknown. KIR 2.1 inward rectifier channels, largely responsible for the cardiac inward rectifier current (IK1 ), are degraded in lysosomes. Amiodarone and dronedarone are class III antiarrhythmics. Chronic use of amiodarone, and to a l...

Tertiapin is a 21-residue peptide isolated from honey bee venoms. A recent study indicated that tertiapin is a potent blocker of certain types of inwardly rectifying K(+) (Kir) channels (). We examined the effect of tertiapin on ion channel currents in rabbit cardiac myocytes using the patch-clamp technique. In the whole-cell configuration, tertiapin fully inhibited acetylcholine (1 microM)-ind...

A fast inwardly rectifying current has been observed in some of the sensory cells (hair cells) of the inner ear of several species. While the current was presumed to be an IKir current, contradictory evidence existed as to whether the cloned channel actually belonged to the Kir 2.0 subfamily of potassium inward rectifiers. In this paper, we report for the first time converging evidence from ele...

Müller cell gliosis is a common response in many retinal pathological conditions. We previously demonstrated that downregulation of Kir channels contributes to Müller cell gliosis in a rat chronic ocular hypertension (COH) model. Here, the possible involvement of outward K+ currents in Müller cell gliosis was investigated. Outward K+ current densities in Müller cells isolated from COH rats, as ...

BACKGROUND/AIMS Mitoxanthrone (MX) is an anthracenedione antineoplastic agent. Whether this drug and other related compounds have any effects on ion currents in osteoclasts remains largely unclear. METHODS In this study, the effects of MX and other related compounds on inwardly rectifying K(+) current (I(K(IR))) were investigated in RAW 264.7 osteoclast precursor cells treated with lipopolysa...

VU590 was the first publicly disclosed, submicromolar-affinity (IC50 = 0.2 μM), small-molecule inhibitor of the inward rectifier potassium (Kir) channel and diuretic target, Kir1.1. VU590 also inhibits Kir7.1 (IC50 ∼ 8 μM), and has been used to reveal new roles for Kir7.1 in regulation of myometrial contractility and melanocortin signaling. Here, we employed molecular modeling, mutagenesis, and...

Inwardly rectifying potassium (K+) channels (Kir) in Müller cells, the dominant glial cells in the retina, are supposed to be responsible for the spatial buffering action of K+ ions. The molecular properties and subcellular localization of Müller cell Kir channels in rat and rabbit retinas were examined by using electrophysiological, molecular biological, and immunostaining techniques. Only a s...

Prokaryotic inwardly rectifying (KirBac) potassium channels are homologous to mammalian Kir channels. Their activity is controlled by dynamical conformational changes that regulate ion flow through a central pore. Understanding the dynamical rearrangements of Kir channels during gating requires high-resolution structure information from channels crystallized in different conformations and insig...