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Kinetic analysis of block of open sodium channels by a peptide containing the isoleucine, phenylalanine, and methionine (IFM) motif from the inactivation gate.

Eaholtz G, Zagotta WN, Catterall WA - J. Gen. Physiol. (1998)

Bottom Line: The apparent Kd was approximately 33 microM at 0 mV.In contrast, the off rates were voltage independent.The results are consistent with the hypothesis that the KIFMK peptide enters the pore of the open sodium channel from the intracellular side and blocks it.

View Article: PubMed Central - PubMed

Affiliation: Graduate Program in Neurobiology, University of Washington, Seattle, Washington 98195, USA.

ABSTRACT
We analyzed the kinetics of interaction between the peptide KIFMK, containing the isoleucine, phen-ylalanine, and methionine (IFM) motif from the inactivation gate, and the brain type IIA sodium channels with a mutation that disrupts inactivation (F1489Q). The on-rate constant was concentration dependent, consistent with a bimolecular reaction with open sodium channels, while the off rates were unaffected by changes in the KIFMK concentration. The apparent Kd was approximately 33 microM at 0 mV. The on rates were voltage dependent, supporting the hypothesis that one or both of the charges in KIFMK enter the membrane electric field. The voltage dependence of block was consistent with the equivalent movement of approximately 0.6 electronic charges across the membrane. In contrast, the off rates were voltage independent. The results are consistent with the hypothesis that the KIFMK peptide enters the pore of the open sodium channel from the intracellular side and blocks it.

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Kinetic analysis of block of open sodium channels by a peptide containing the isoleucine, phenylalanine, and methionine (IFM) motif from the inactivation gate.

Eaholtz G, Zagotta WN, Catterall WA - J. Gen. Physiol. (1998)

© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC1887774&req=5

Bottom Line: The apparent Kd was approximately 33 microM at 0 mV.In contrast, the off rates were voltage independent.The results are consistent with the hypothesis that the KIFMK peptide enters the pore of the open sodium channel from the intracellular side and blocks it.

View Article: PubMed Central - PubMed

Affiliation: Graduate Program in Neurobiology, University of Washington, Seattle, Washington 98195, USA.

ABSTRACT
We analyzed the kinetics of interaction between the peptide KIFMK, containing the isoleucine, phen-ylalanine, and methionine (IFM) motif from the inactivation gate, and the brain type IIA sodium channels with a mutation that disrupts inactivation (F1489Q). The on-rate constant was concentration dependent, consistent with a bimolecular reaction with open sodium channels, while the off rates were unaffected by changes in the KIFMK concentration. The apparent Kd was approximately 33 microM at 0 mV. The on rates were voltage dependent, supporting the hypothesis that one or both of the charges in KIFMK enter the membrane electric field. The voltage dependence of block was consistent with the equivalent movement of approximately 0.6 electronic charges across the membrane. In contrast, the off rates were voltage independent. The results are consistent with the hypothesis that the KIFMK peptide enters the pore of the open sodium channel from the intracellular side and blocks it.

Show MeSH
Related in: MedlinePlus