Activation properties of Kv4.3 channels: time, voltage and [K<sup>+</sup>]<sub>o</sub> dependence

Wang, Shimin; Bondarenko, Vladimir E.; Qu, Yujie; Morales, Michael J.; Rasmusson, Randall L.; Strauss, Harold C.

doi:10.1113/jphysiol.2003.058578

Cited by 34 publications

(57 citation statements)

References 57 publications

(105 reference statements)

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“…This compensation gives similar results obtained during the development of our original Kv4.3 model (Wang et al, 2004), suggesting that it is valid for Kv4.1 activation as well. To model the effect of HpTx2 on Kv4.1 and Kv4.3, we assumed that one toxin molecule could bind to each subunit and that each subunit activates independently.…”

Section: Resultssupporting

confidence: 69%

“…To test this hypothesis, we took our previously described Markov model of Kv4.3 activation (Wang et al, 2004), and used experimentally derived data to develop a Markov model of Kv4.1 activation. The Markov model structure for activation in the absence of HpTx2 is described in scheme 1 (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Two-Electrode Voltage-Clamp Technique. Currents were measured in oocytes using a two-microelectrode Dagan CA-1B amplifier as described previously (Wang et al, 2004;Wang et al, 2005). Electrodes were filled with 3 M KCl.…”

Section: Methodsmentioning

confidence: 99%

“…The numerical solution of differential equations was performed by a fourth-order RungeKutta method. Channel models were allowed to run for at least 600 s to calculate the steady-state values of occupancies of channel states and were used as the initial conditions (Wang et al, 2004).…”

Section: Methodsmentioning

confidence: 99%

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Heteropoda Toxin 2 Interaction with Kv4.3 and Kv4.1 Reveals Differences in Gating Modification

DeSimone

Zarayskiy²,

Bondarenko³

et al. 2011

Mol Pharmacol

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Kv4 (Shal) potassium channels are responsible for the transient outward K ϩ currents in mammalian hearts and central nervous systems. Heteropoda toxin 2 (HpTx2) is an inhibitor cysteine knot peptide toxin specific for Kv4 channels that inhibits gating of Kv4.3 in the voltage-dependent manner typical for this type of toxin. HpTx2 interacts with four independent binding sites containing two conserved hydrophobic amino acids in the S3b transmembrane segments of Kv4.3 and the closely related Kv4.1. Despite these similarities, HpTx2 interaction with Kv4.1 is considerably less voltage-dependent, has smaller shifts in the voltage-dependences of conductance and steady-state inactivation, and a 3-fold higher K d value. Swapping four nonconserved amino acids in S3b between the two channels exchanges the phenotypic response to HpTx2. To understand these differences in gating modification, we constructed Markov models of Kv4.3 and Kv4.1 activation gating in the presence of HpTx2. Both models feature a series of voltagedependent steps leading to a final voltage-independent transition to the open state and closely replicate the experimental data. Interaction with HpTx2 increases the energy barrier for channel opening by slowing activation and accelerating deactivation. The greater degree of voltage-dependence in Kv4.3 occurs because it is the voltage-dependent transitions that are most affected by HpTx2; in contrast, it is the voltage-independent step in Kv4.1 that is most affected by the presence of toxin. These data demonstrate the basis for subtype-specificity of HpTx2 and point the way to a general model of gating modifier toxin interaction with voltage-gated ion channels.

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Section: Resultssupporting

confidence: 69%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

Heteropoda Toxin 2 Interaction with Kv4.3 and Kv4.1 Reveals Differences in Gating Modification

DeSimone

Zarayskiy²,

Bondarenko³

et al. 2011

Mol Pharmacol

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“…WT cDNA of Kv4.3 (short form) was a gift of Dr. David McKinnon (State University of New York at Stony Brook), and its use has been previously described (73). Synthetic mRNA was prepared using an mMESSAGE mMACHINE T7 kit (Ambion, Austin, TX).…”

Section: Methodsmentioning

confidence: 99%

W-7 modulates K_v4.3: pore block and Ca²⁺-calmodulin inhibition

Bondarenko²,

Xie³

et al. 2007

American Journal of Physiology-Heart and Circulatory Physiology

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K+ Channels of Squid Giant Axons Open by an Osmotic Stress in Hypertonic Solutions Containing Nonelectrolytes

Kukita

2011

J Membrane Biol

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In hypertonic solutions made by adding nonelectrolytes, K(+) channels of squid giant axons opened at usual asymmetrical K(+) concentrations in two different time courses; an initial instantaneous activation (I (IN)) and a sigmoidal activation typical of a delayed rectifier K(+) channel (I (D)). The current-voltage relation curve for I (IN) was fitted well with Goldman equation described with a periaxonal K(+) concentration at the membrane potential above -10 mV. Using the activation-voltage curve obtained from tail currents, K(+) channels for I (IN) are confirmed to activate at the membrane potential that is lower by 50 mV than those for I (D). Both I (IN) and I (D) closed similarly at the holding potential below -100 mV. The logarithm of I (IN)/I (D) was linearly related with the osmolarity for various nonelectrolytes. Solute inaccessible volumes obtained from the slope increased with the nonelectrolyte size from 15 to 85 water molecules. K(+) channels representing I (D) were blocked by open channel blocker tetra-butyl ammonium (TBA) more efficiently than in the absence of I (IN), which was explained by the mechanism that K(+) channels for I (D) were first converted to those for I (IN) by the osmotic pressure and then blocked. So K(+) channels for I (IN) were suggested to be derived from the delayed rectifier K(+) channels. Therefore, the osmotic pressure is suggested to exert delayed-rectifier K(+) channels to open in shrinking rather hydrophilic flexible parts outside the pore than the pore itself, which is compatible with the recent structure of open K(+) channel pore.

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Activation properties of Kv4.3 channels: time, voltage and [K⁺]_o dependence

Cited by 34 publications

References 57 publications

Heteropoda Toxin 2 Interaction with Kv4.3 and Kv4.1 Reveals Differences in Gating Modification

Heteropoda Toxin 2 Interaction with Kv4.3 and Kv4.1 Reveals Differences in Gating Modification

W-7 modulates K_v4.3: pore block and Ca²⁺-calmodulin inhibition

K+ Channels of Squid Giant Axons Open by an Osmotic Stress in Hypertonic Solutions Containing Nonelectrolytes

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Activation properties of Kv4.3 channels: time, voltage and [K+]o dependence

Cited by 34 publications

References 57 publications

Heteropoda Toxin 2 Interaction with Kv4.3 and Kv4.1 Reveals Differences in Gating Modification

Heteropoda Toxin 2 Interaction with Kv4.3 and Kv4.1 Reveals Differences in Gating Modification

W-7 modulates Kv4.3: pore block and Ca2+-calmodulin inhibition

K+ Channels of Squid Giant Axons Open by an Osmotic Stress in Hypertonic Solutions Containing Nonelectrolytes

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Activation properties of Kv4.3 channels: time, voltage and [K⁺]_o dependence

W-7 modulates K_v4.3: pore block and Ca²⁺-calmodulin inhibition