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Isolation of Human Atrial Myocytes for Simultaneous Measurements of Ca2+ Transients and Membrane Currents
10:53

Isolation of Human Atrial Myocytes for Simultaneous Measurements of Ca2+ Transients and Membrane Currents

Published on: July 3, 2013

Transient-outward K+ channel inhibition facilitates L-type Ca2+ current in heart

Yanggan Wang1, Jun Cheng, Samvit Tandan

  • 1Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA. yanggan.wang@utsouthwestern.edu

Journal of Cardiovascular Electrophysiology
|April 29, 2006
PubMed
Abstract

Insights

4-aminopyridine (4-AP), an I(to) channel blocker, enhances cardiac L-type calcium current (I(Ca)) by activating CaMKII. This study reveals a functional link between I(to) and I(Ca) in heart cells.

Area of Science:

  • Cardiology
  • Molecular Biology
  • Electrophysiology

Background:

  • Transient outward current (I(to)) and L-type calcium current (I(Ca)) are crucial for cardiac repolarization.
  • Disease-related remodeling of I(to) and I(Ca) suggests a functional coupling.
  • Investigated the impact of I(to) channel blockers on I(Ca) in ventricular myocytes.

Purpose of the Study:

  • To determine the effects of 4-aminopyridine (4-AP) and heteropodatoxin-2 (HpTx2) on I(Ca).
  • To elucidate the underlying mechanisms of I(to) and I(Ca) interaction.

Main Methods:

  • Whole-cell voltage clamp recordings in mouse and guinea pig ventricular myocytes.
  • Utilized 4-AP as an I(to) blocker and KN93 to inhibit CaMKII.
  • Measured Ca2+/calmodulin-dependent protein kinase (CaMKII) activity.

Main Results:

  • 4-AP significantly facilitated I(Ca) in mouse myocytes by increasing amplitude and slowing inactivation.
  • These effects were independent of Ca2+ influx and voltage.
  • 4-AP-induced I(Ca) facilitation was abolished by CaMKII inhibition (KN93).
  • 4-AP had no effect on I(Ca) in guinea pig myocytes, which lack I(to).
  • 4-AP blocked Ca2+-induced I(Ca) facilitation in mouse but not guinea pig myocytes.

Conclusions:

  • 4-AP facilitates I(Ca) via a mechanism involving the I(to) channel and CaMKII activation.
  • These findings demonstrate a functional association between I(Ca) and I(to) in cardiac myocytes.

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