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Related Experiment Videos

Age associated changes in membrane currents in rat ventricular myocytes

K E Walker1, E G Lakatta, S R Houser

  • 1Department of Medicine, Medical College of Pennsylvania, Philadelphia.

Cardiovascular Research
|November 1, 1993
PubMed
Summary

Aging prolongs rat heart action potentials due to slowed L-type calcium current inactivation and reduced transient outward potassium current density. Buffering intracellular calcium normalized these age-related changes.

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Area of Science:

  • Cardiology
  • Electrophysiology
  • Aging Research

Background:

  • Senescent rat ventricular myocytes exhibit prolonged action potential duration compared to young adults.
  • Age-related changes in ion channel function may underlie these electrophysiological alterations.

Purpose of the Study:

  • To investigate the roles of L-type calcium current (ICa), transient outward potassium current (ITO), and inwardly rectifying potassium current (IK1) in age-related action potential prolongation.
  • To determine if altered ICa and ITO contribute to the extended early and late phases of the action potential plateau in senescent rats.

Main Methods:

  • Whole-cell voltage clamp electrophysiology was employed.
  • Ventricular myocytes were isolated from young (2-3 months), middle-aged (8-9 months), and senescent (24-25 months) rats.

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  • Ionic currents (ICa, ITO) were analyzed for magnitude, voltage dependence, and kinetic properties.

    • Main Results:

    • L-type calcium current (ICa) density and voltage dependence remained unchanged with age, but its inactivation slowed significantly in senescent rats.
    • Peak transient outward potassium current (ITO) density decreased with age, with minor slowing of inactivation kinetics.
    • Buffering intracellular calcium with EGTA abolished age-related differences in action potential duration and ICa inactivation.

    Conclusions:

    • While ICa density is preserved, slowed inactivation contributes to action potential prolongation in aging rats.
    • Reduced ITO channel density also plays a role in the electrophysiological changes observed with senescence.
    • Intracellular calcium handling is a key factor in the age-associated modifications of cardiac action potential duration.