Polyamine Permeation and Rectification of Kir4.1 Channels

Kucheryavykh, Yury V.; Pearson, Wade L.; Kurata, Harley T.; Eaton, Misty J.; Skatchkov, Serguei N.; Nichols, Colin G.

doi:10.4161/chan.4389

Cited by 29 publications

(32 citation statements)

References 37 publications

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“…The simplest interpretation is that these maneuvers increase the rate of blocker dissociation into the cytoplasmic compartment via ionblocker interactions within the intracellular pore. VU590 actions on the extracellular pore with blocker "punchthrough" (Kucheryavykh et al, 2007) is also conceivable, but seems less likely given the recent identification of low potency cytoplasmic Kir channel inhibitors exhibiting similar electrophysiological profiles. Tricyclic antidepressants such as nortriptyline block Kir4.1 channels with IC 50 values in the 20 to 100 M range (Furutani et al, 2009), whereas the antimalarial agent chloroquine inhibits Kir2.1 with an IC 50 of ϳ10 M (Rodríguez- Menchaca et al, 2008).…”

Section: Discussionmentioning

confidence: 99%

High-Throughput Screening Reveals a Small-Molecule Inhibitor of the Renal Outer Medullary Potassium Channel and Kir7.1

Lewis

Bhave²,

Chauder³

et al. 2009

Mol Pharmacol

114

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Section: Discussionmentioning

confidence: 99%

High-Throughput Screening Reveals a Small-Molecule Inhibitor of the Renal Outer Medullary Potassium Channel and Kir7.1

Lewis

Bhave²,

Chauder³

et al. 2009

Mol Pharmacol

114

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“…(1)], wherein intracellular SP blocks outward current through a fraction of K 1 channels with a spermine-insensitive time-and voltage-independent component of K 1 conductance. This may be due to some intrinsic processes of K 1 -channels, such as TASK (Skatchkov et al, 2006) and small leakage through the unblocked fraction of Kir4.1 (Kucheryavykh et al, 2007b). If such spermine-insensitive timeand voltage-independent component of K 1 conductance was subtracted, two different components of SP block, fast and slow, were evident (Fig.…”

Section: Intracellular Sp Blocks a Fraction Ofmentioning

confidence: 98%

Complex rectification of Müller cell Kir currents

Kucheryavykh

Shuba

Антонов

et al. 2008

Glia

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Although Kir4.1 channels are the major inwardly rectifying channels in glial cells and are widely accepted to support K+- and glutamate-uptake in the nervous system, the properties of Kir4.1 channels during vital changes of K+ and polyamines remain poorly understood. Therefore, the present study examined the voltage-dependence of K+ conductance with varying physiological and pathophysiological external [K+] and intrapipette spermine ([SP]) concentrations in Müller glial cells and in tsA201 cells expressing recombinant Kir4.1 channels. Two different types of [SP] block were characterized: "fast" and "slow." Fast block was steeply voltage-dependent, with only a low sensitivity to spermine and strong dependence on extracellular potassium concentration, [K+]o. Slow block had a strong voltage sensitivity that begins closer to resting membrane potential and was essentially [K+]o-independent, but with a higher spermine- and [K+]i-sensitivity. Using a modified Woodhull model and fitting i/V curves from whole cell recordings, we have calculated free [SP](in) in Müller glial cells as 0.81 +/- 0.24 mM. This is much higher than has been estimated previously in neurons. Biphasic block properties underlie a significantly varying extent of rectification with [K+] and [SP]. While confirming similar properties of glial Kir and recombinant Kir4.1, the results also suggest mechanisms underlying K+ buffering in glial cells: When [K+]o is rapidly increased, as would occur during neuronal excitation, "fast block" would be relieved, promoting potassium influx to glial cells. Increase in [K+]in would then lead to relief of "slow block," further promoting K+-influx.

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“…COSm6 Cells-pEGFP-rKir4.1, in which rat Kir4.1 cDNA is fused to a N-terminal EGFP 2 tag (36), was used as template into which EAST/SeSAME mutations were introduced, by means of the QuikChange II site-directed mutagenesis kit (Stratagene). The integrity of all of the constructs was verified by sequencing.…”

Section: Expression Of Wild-type and Mutant Kir41 Channels Inmentioning

confidence: 99%