Modulation of C-Type Inactivation by K+ at the Potassium Channel Selectivity Filter

Kiss, László; Korn, Stephen J.

doi:10.1016/s0006-3495(98)77894-4

Cited by 139 publications

(144 citation statements)

References 29 publications

(60 reference statements)

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“…In our model, as in its predecessors, the inactivation time constant of the model A-type current is 150 ms (Bhalla and Bower 1993), a value intermediate between the ranges associated with classical fast-inactivating A current and those associated with its slower, putative variant known as D current (Wu and Barish 1992), but certainly reflecting the slower C-type inactivation mechanism nominally characteristic of the latter (Fadool and Levitan 1998; see also Kiss and Korn 1998). Direct measurements of the inactivation time constant for total endogenous A/D-like currents in mitral cells vary [45 ms (Wang et al 1996); 90 ms ; 40 -500 ms (Balu et al 2004)], and it has been proposed that both A-and D-like currents-or, equivalently, a heterogeneous population of inactivating potassium currents-are maintained in mitral cells (Balu et al 2004;Chen and Shepherd 1997).…”

Section: Slow Processes Regulating Burst Propertiesmentioning

confidence: 78%

Dynamical Mechanisms of Odor Processing in Olfactory Bulb Mitral Cells

Rubin

Cleland²

2006

Journal of Neurophysiology

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Rubin, Daniel B. and Thomas A. Cleland. Dynamical mechanisms of odor processing in olfactory bulb mitral cells. J Neurophysiol 96: 555-568, 2006. First published May 17, 2006 doi:10.1152/jn.00264.2006. In the olfactory system, the contribution of dynamical properties such as neuronal oscillations and spike synchronization to the representation of odor stimuli is a matter of substantial debate. While relatively simple computational models have sufficed to guide current research in large-scale network dynamics, less attention has been paid to modeling the membrane dynamics in bulbar neurons that may be equally essential to sensory processing. We here present a reduced, conductance-based compartmental model of olfactory bulb mitral cells that exhibits the complex dynamical properties observed in these neurons. Specifically, model neurons exhibit intrinsic subthreshold oscillations with voltage-dependent frequencies that shape the timing of stimulus-evoked action potentials. These oscillations rely on a persistent sodium conductance, an inactivating potassium conductance, and a calcium-dependent potassium conductance and are reset via inhibitory input such as that delivered by periglomerular cell shunt inhibition. Mitral cells fire bursts, or clusters, of spikes when continuously stimulated. Burst properties depend critically on multiple currents, but a progressive deinactivation of I A over the course of a burst is an important regulator of burst termination. Each of these complex properties exhibits appropriate dynamics and pharmacology as determined by electrophysiological studies. Additionally, we propose that a second, inconsistently observed form of infrathreshold bistability in mitral cells may derive from the activation of ATP-activated potassium currents responding to hypoxic conditions. We discuss the integration of these cellular properties in the larger context of olfactory bulb network operations.

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Section: Slow Processes Regulating Burst Propertiesmentioning

confidence: 78%

Dynamical Mechanisms of Odor Processing in Olfactory Bulb Mitral Cells

Rubin

Cleland²

2006

Journal of Neurophysiology

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“…This model is supported by functional analysis through K + depletion experiments and a change in selectivity when K + is removed from the channel (López-Barneo et al, 1993;Kiss and Korn, 1998), indicating a partial collapse of the selectivity filter (Yellen, 1998), although other measurements suggest that the C-type I state of the channel is not identical to the K + -removed state of the channel (Jäger et al, 1998).…”

Section: Introductionmentioning

confidence: 93%

Effect of verapamil on the action of methanethiosulfonate reagents on human voltage‐gated K_v1.3 channels: implications for the C‐type inactivated state

Schmid

Grissmer

2011

British J Pharmacology

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BACKGROUND AND PURPOSEVoltage-gated Kv1.3 channels appear on T-lymphocytes and are characterized by their typical C-type inactivation. In order to develop drugs stabilizing the C-type inactivated state and thus potentially useful in treatment of autoimmune diseases, it is important to know more about the three-dimensional structure of this inactivated state of the channel. EXPERIMENTAL APPROACHThe patch-clamp technique was used to study effects of methanethiosulphonate (MTS) compounds on currents through wild-type human Kv1.3 (hKv1.3) and two mutant channels, hKv1.3 V417C and hKv1.3 H399T-V417C, in the closed, open and inactivated states. KEY RESULTSExtracellular application of 2-aminoethyl methanethiosulphonate (MTSEA) irreversibly reduced currents through hKv1.3 V417C channels in the open and inactivated, but not in the closed state, indicating that a modification was possible. Co-application of verapamil prevented this reduction. Intracellular application of MTSEA and [2-(trimethylammonium)ethyl] methanethiosulphonate (MTSET) also modified the mutant channels, whereas extra-and intracellular application of sodium (2-sulfonatoethyl)methanethiosulphonate (MTSES) and intracellular application of MTSET did not. CONCLUSIONS AND IMPLICATIONSOur experiments showed that the binding site for MTS compounds was intracellular in the mutant channels and that the V417C mutant channels were modified in the open and the inactivated states, and this modification was prevented by verapamil. Therefore, the activation gate on the intracellular side of the selectivity filter must be open during inactivation. Furthermore, although the S6 segment is moving further apart during inactivation, this change does not include a movement of the side chain of the amino acid at position 417, away from lining the channel pore. Abbreviations

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“…Previous studies have shown that pore mutations in Shaker K ϩ channels can alter rates of channel closing and C-type inactivation (Molina et al, 1998;Rasmusson et al, 1998). Notably, the latter is thought to be mediated by direct constriction (or "collapse") of the pore itself, and this process can be slowed by occupation of the pore by permeant ions (Kiss and Korn, 1998;Molina et al, 1998;Rasmusson et al, 1998).…”

Section: Pore Site Modulates Nmdar Gating 161mentioning

confidence: 99%

Site withinN-Methyl-d-aspartate Receptor Pore Modulates Channel Gating

Chen¹,

Li²,

Murphy³

et al. 2004

Mol Pharmacol

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N-methyl-D-aspartate-type glutamate receptors (NMDARs) are ligand-gated ion channels activated by coagonists glutamate and glycine. NMDARs play a critical role in synaptic plasticity and excitotoxicity, largely because of their high calcium permeability and slow deactivation and desensitization kinetics. NR1 is an obligate subunit in all NMDAR complexes, where it combines with NR2A, 2B, 2C, and/or 2D. NR1 binds glycine, and residue Asn598 in the re-entrant membrane loop M2 largely determines NMDAR calcium permeability. In contrast, NR2 subunits bind glutamate and contain regions that regulate receptor desensitization and deactivation. Here, we report that mutations of NR1(Asn598) in combination with wild-type NR2A, expressed in human embryonic kidney 293 cells, exhibit altered glycine-independent desensitization. In the absence of extracellular calcium, substitution of Arg for Asn598 (NR1R) slowed desensitization by 2-to 3-fold compared with wild-type NR1/ NR2A, and glutamate-evoked peak current EC 50 and deactivation rate were also affected. Replacement of Asn by Gln (NR1Q) produced two distinct rates of calcium-and glycine-independent desensitization. Moreover, in the presence of extracellular calcium, the voltage-dependent pore block by calcium for the NR1Q mutant mimicked the effects of the positively charged Arg at this site in NR1R on slowing desensitization and deactivation. A kinetic model of the NMDA receptor-channel suggests that these results can be explained by altered gating and not ligand binding. Our data increase understanding of the role that amino acids within the NMDAR pore play in channel gating.

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Modulation of C-Type Inactivation by K+ at the Potassium Channel Selectivity Filter

Cited by 139 publications

References 29 publications

Dynamical Mechanisms of Odor Processing in Olfactory Bulb Mitral Cells

Dynamical Mechanisms of Odor Processing in Olfactory Bulb Mitral Cells

Effect of verapamil on the action of methanethiosulfonate reagents on human voltage‐gated K_v1.3 channels: implications for the C‐type inactivated state

Site withinN-Methyl-d-aspartate Receptor Pore Modulates Channel Gating

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Modulation of C-Type Inactivation by K+ at the Potassium Channel Selectivity Filter

Cited by 139 publications

References 29 publications

Dynamical Mechanisms of Odor Processing in Olfactory Bulb Mitral Cells

Dynamical Mechanisms of Odor Processing in Olfactory Bulb Mitral Cells

Effect of verapamil on the action of methanethiosulfonate reagents on human voltage‐gated Kv1.3 channels: implications for the C‐type inactivated state

Site withinN-Methyl-d-aspartate Receptor Pore Modulates Channel Gating

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Effect of verapamil on the action of methanethiosulfonate reagents on human voltage‐gated K_v1.3 channels: implications for the C‐type inactivated state