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

Published

Journal Article

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 delta KPQ mutation has multiple effects on activation and inactivation. The aggregate effects may account for the increased susceptibility to arrhythmias.

Full Text

Duke Authors

Cited Authors

  • Chandra, R; Starmer, CF; Grant, AO

Published Date

  • May 1998

Published In

Volume / Issue

  • 274 / 5

Start / End Page

  • H1643 - H1654

PubMed ID

  • 9612375

Pubmed Central ID

  • 9612375

Electronic International Standard Serial Number (EISSN)

  • 2163-5773

International Standard Serial Number (ISSN)

  • 0002-9513

Digital Object Identifier (DOI)

  • 10.1152/ajpheart.1998.274.5.h1643

Language

  • eng