Effect of extracellular cations on the inward rectifying K+ channels Kir2.1 and Kir3.1/Kir3.4

Owen, Jenny; Quinn, Claire C.; Leach, Robert; Findlay, Jbc; Boyett, Mark R.

doi:10.1017/s0958067099018060

Cited by 16 publications

(22 citation statements)

References 4 publications

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“…Fig. 5B shows that Ba 2ϩ block of the wild-type channel was voltage-dependent and Ba 2ϩ sensitivity was greater at more negative potentials, as shown previously (21). For the wild-type channel, ␦ was 0.31 Ϯ 0.01 (n ϭ 10).…”

Section: Effect Of H5 Mutations On Slowsupporting

confidence: 82%

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Residues and Mechanisms for Slow Activation and Ba2+Block of the Cardiac Muscarinic K+ Channel, Kir3.1/Kir3.4

Lancaster¹,

Dibb²,

Quinn³

et al. 2000

Journal of Biological Chemistry

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Mechanisms and residues responsible for slow activation and Ba 2؉ block of the cardiac muscarinic K ؉ channel, Kir3.1/Kir3.4, were investigated using site-directed mutagenesis. Mutagenesis of negatively charged residues located throughout the pore of the channel (in H5, M2, and proximal C terminus) reduced or abolished slow activation. The strongest effects resulted from mutagenesis of residues in H5 close to the selectivity filter; mutagenesis of residues in M2 and proximal C terminus equivalent to those identified as important determinants of the activation kinetics of Kir2.1 was less effective. In giant patches, slow activation was present in cell-attached patches, lost on excision of the patch, and restored on perfusion with polyamine. Mutagenesis of residues in H5 and M2 close to the selectivity filter also decreased Ba 2؉ block of the channel. A critical residue for Ba 2؉ block was identified in Kir3.4. Mutagenesis of the equivalent residue in Kir3.1 failed to have as pronounced an effect on Ba 2؉ block, suggesting an asymmetry of the channel pore. It is concluded that slow activation is principally the result of unbinding of polyamines from negatively charged residues close to the selectivity filter of the channel and not an intrinsic gating mechanism. Ba 2؉ block involves an interaction with the same residues.

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Section: Effect Of H5 Mutations On Slowsupporting

confidence: 82%

“…Stock solutions of cRNA were diluted in nuclease-free water to give the appropriate concentrations prior to injection. Oocyte preparation, injection of RNA, and two-microelectrode voltage clamp recordings were performed as described previously (21). The bath solution contained (in mM): KCl 90, HEPES 5, CaCl 2 2, pH 7.4 (KOH).…”

mentioning

confidence: 99%

Residues and Mechanisms for Slow Activation and Ba2+Block of the Cardiac Muscarinic K+ Channel, Kir3.1/Kir3.4

Lancaster¹,

Dibb²,

Quinn³

et al. 2000

Journal of Biological Chemistry

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“…5). In addition, while GIRK (K ir 3.x) channels are also expressed within lamina I–II (Luscher et al, 1997; Marker et al, 2005; Marker et al, 2006) and highly sensitive to Ba 2+ (Owen et al, 1999; Lancaster et al, 2000), we found no evidence that these channels were constitutively active in SDH neurons at this age. This implies that differences in GIRK expression between the pacemaker and non-pacemaker populations are unlikely to explain the lower K ir conductance seen in spontaneously bursting neurons.…”

Section: Discussioncontrasting

confidence: 67%

Inward-Rectifying Potassium (K_ir) Channels Regulate Pacemaker Activity in Spinal Nociceptive Circuits during Early Life

Blankenship

Baccei

2013

J. Neurosci.

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Pacemaker neurons in neonatal spinal nociceptive circuits generate intrinsic burst-firing and are distinguished by a lower “leak” membrane conductance compared to adjacent, non-bursting neurons. However, little is known about which subtypes of leak channels regulate the level of pacemaker activity within the developing rat superficial dorsal horn (SDH). Here we demonstrate that a hallmark feature of lamina I pacemaker neurons is a reduced conductance through inward-rectifying potassium (Kir) channels at physiological membrane potentials. Differences in the strength of inward rectification between pacemakers and non-pacemakers indicate the presence of functionally distinct Kir currents in these two populations at room temperature. However, Kir currents in both groups showed high sensitivity to block by extracellular Ba2+ (IC50 ~ 10 µM), which suggests the presence of ‘classical’ Kir (Kir2.x) channels in the neonatal SDH. The reduced Kir conductance within pacemakers is unlikely to be explained by an absence of particular Kir2.x isoforms, as immunohistochemical analysis revealed the expression of Kir2.1, Kir2.2 and Kir2.3 within spontaneously bursting neurons. Importantly, Ba2+ application unmasked rhythmic burst-firing in ~42% of non-bursting lamina I neurons, suggesting that pacemaker activity is a latent property of a sizeable population of SDH cells during early life. In addition, the prevalence of spontaneous burst-firing within lamina I was enhanced in the presence of high internal concentrations of free Mg2+, consistent with its documented ability to block Kir channels from the intracellular side. Collectively, the results indicate that Kir channels are key modulators of pacemaker activity in newborn central pain networks.

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“…It has been reported that external calcium, as well as other divalent cations, can block IRK (including K ir 3.1 and 3.4) channels (Owen et al, 1999). However there is no complete characterization of any direct inhibition of GIRK by intracellularly positioned calcium ions.…”

Section: Discussionmentioning

confidence: 99%

Calcium Release from Stores Inhibits GIRK

Kramer

Williams

2016

Cell Reports

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Summary Synaptic transmission is mediated by ionotropic and metabotropic receptors that together regulate the rate and pattern of action potential firing. Metabotropic receptors can activate ion channels and modulate other receptors and channels. The present paper examines the interaction between group 1 mGluR-mediated calcium release from stores, and GABAB/D2 mediated GIRK currents in rat dopamine neurons of the Substantia Nigra. Transient activation of mGluRs decreased the GIRK current evoked by GABAB and D2 receptors, though less efficaciously for D2. The mGluR-induced inhibition of GIRK current peaked in 1 second and recovered to baseline after 5 seconds. The inhibition was dependent on release of calcium from stores, was larger for transient than for tonic currents, and was unaffected by inhibitors of PLC, PKC, PLA2, or calmodulin. This inhibition of GABAB IPSCs through release of calcium from stores is a postsynaptic mechanism that may broadly reduce GIRK-dependent inhibition of many central neurons.

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Effect of extracellular cations on the inward rectifying K+ channels Kir2.1 and Kir3.1/Kir3.4

Cited by 16 publications

References 4 publications

Residues and Mechanisms for Slow Activation and Ba2+Block of the Cardiac Muscarinic K+ Channel, Kir3.1/Kir3.4

Residues and Mechanisms for Slow Activation and Ba2+Block of the Cardiac Muscarinic K+ Channel, Kir3.1/Kir3.4

Inward-Rectifying Potassium (K_ir) Channels Regulate Pacemaker Activity in Spinal Nociceptive Circuits during Early Life

Calcium Release from Stores Inhibits GIRK

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Effect of extracellular cations on the inward rectifying K+ channels Kir2.1 and Kir3.1/Kir3.4

Cited by 16 publications

References 4 publications

Residues and Mechanisms for Slow Activation and Ba2+Block of the Cardiac Muscarinic K+ Channel, Kir3.1/Kir3.4

Residues and Mechanisms for Slow Activation and Ba2+Block of the Cardiac Muscarinic K+ Channel, Kir3.1/Kir3.4

Inward-Rectifying Potassium (Kir) Channels Regulate Pacemaker Activity in Spinal Nociceptive Circuits during Early Life

Calcium Release from Stores Inhibits GIRK

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Inward-Rectifying Potassium (K_ir) Channels Regulate Pacemaker Activity in Spinal Nociceptive Circuits during Early Life