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Multiple effects of KPQ deletion mutation on gating of human cardiac Na+channels expressed in mammalian cells.

Publication ,  Journal Article
Chandra, R; Starmer, CF; Grant, AO
Published in: Am J Physiol Heart Circ Physiol
May 1, 1998

Several aspects of the effect of the KPQ deletion mutation on Na+channel gating remain unresolved. We have analyzed the kinetics of the early and late currents by recording whole cell and single-channel currents in a human embryonic kidney (HEK) cell line (HEK293) expressing wild-type and KPQ deletion mutation in cardiac Na+channels. The rate of inactivation increased three- to fivefold between -40 and -80 mV in the mutant channel. The rate of recovery from inactivation was increased twofold. Two modes of gating accounted for the late current: 1) isolated brief openings with open times that were weakly voltage dependent and the same as the initial transient and 2) bursts of opening with highly voltage-dependent prolonged open times. Latency to first opening was accelerated, suggesting an acceleration of the rate of activation. The ΔKPQ mutation has multiple effects on activation and inactivation. The aggregate effects may account for the increased susceptibility to arrhythmias.

Duke Scholars

Published In

Am J Physiol Heart Circ Physiol

DOI

EISSN

1522-1539

Publication Date

May 1, 1998

Volume

274

Issue

5

Start / End Page

H1643 / H1654

Location

United States

Related Subject Headings

  • Sodium Channels
  • Sequence Deletion
  • Long QT Syndrome
  • Ion Channel Gating
  • Humans
  • Heart
  • Genetic Predisposition to Disease
  • Electrophysiology
  • Cell Line
  • Cardiovascular System & Hematology
 

Citation

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Chandra, R., Starmer, C. F., & Grant, A. O. (1998). Multiple effects of KPQ deletion mutation on gating of human cardiac Na+channels expressed in mammalian cells. Am J Physiol Heart Circ Physiol, 274(5), H1643–H1654. https://doi.org/10.1152/ajpheart.1998.274.5.H1643
Chandra, Rashmi, C Frank Starmer, and Augustus O. Grant. “Multiple effects of KPQ deletion mutation on gating of human cardiac Na+channels expressed in mammalian cells.Am J Physiol Heart Circ Physiol 274, no. 5 (May 1, 1998): H1643–54. https://doi.org/10.1152/ajpheart.1998.274.5.H1643.
Chandra R, Starmer CF, Grant AO. Multiple effects of KPQ deletion mutation on gating of human cardiac Na+channels expressed in mammalian cells. Am J Physiol Heart Circ Physiol. 1998 May 1;274(5):H1643–54.
Chandra, Rashmi, et al. “Multiple effects of KPQ deletion mutation on gating of human cardiac Na+channels expressed in mammalian cells.Am J Physiol Heart Circ Physiol, vol. 274, no. 5, May 1998, pp. H1643–54. Pubmed, doi:10.1152/ajpheart.1998.274.5.H1643.
Chandra R, Starmer CF, Grant AO. Multiple effects of KPQ deletion mutation on gating of human cardiac Na+channels expressed in mammalian cells. Am J Physiol Heart Circ Physiol. 1998 May 1;274(5):H1643–H1654.

Published In

Am J Physiol Heart Circ Physiol

DOI

EISSN

1522-1539

Publication Date

May 1, 1998

Volume

274

Issue

5

Start / End Page

H1643 / H1654

Location

United States

Related Subject Headings

  • Sodium Channels
  • Sequence Deletion
  • Long QT Syndrome
  • Ion Channel Gating
  • Humans
  • Heart
  • Genetic Predisposition to Disease
  • Electrophysiology
  • Cell Line
  • Cardiovascular System & Hematology