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Mechanism for action potential alternans: the interplay between L-type calcium current and transient outward current.

Abstract：

BACKGROUND:The ionic mechanisms underlying action potential duration alternans are not established. OBJECTIVES:The purpose of this study was to explore the mechanisms underlying action potential alternans. METHODS:Computer simulations were performed using a model of a single ischemic myocyte. To emulate ischemia, extracellular potassium was raised to 10 mM, L-type calcium channel conductance was decreased, and the conductivity of the transient outward current I(to)was varied. RESULTS:Alternans occurred at basic cycle lengths between 350 and 1,800 ms. The alternans resulted from the interplay of the recovery kinetics of the calcium and transient outward current inactivation gates. Depending on the diastolic interval, the transient outward current was sufficiently strong and calcium current sufficiently weak to result in the abolition of the action potential plateau and thus in an abbreviated action potential. The inactivation and recovery kinetics of the inactivation gates were such that calcium current was relatively stronger than transient outward current after an abbreviated action potential. The subsequent action potential was long because calcium current was sufficiently large to restore the action potential plateau dome after the partial repolarization caused by the transient outward current. The long-short pattern repeated indefinitely. This alternans mechanism explains how 2:1 patterns can evolve into 3:1 patterns, as observed in at least one experiment, as ischemia progresses and calcium current diminishes. CONCLUSION:Computer simulations and basic theory suggest that the interplay between L-type calcium and transient outward currents causes at least one type of alternans.

journal_name

Heart Rhythm

journal_title

Heart rhythm

authors

Hopenfeld B

doi

10.1016/j.hrthm.2005.11.016

keywords:

subject

Has Abstract

pub_date

2006-03-01 00:00:00

pages

345-52

issue

3

eissn

1547-5271

issn

1556-3871

pii

S1547-5271(05)02350-7

journal_volume

3

pub_type

杂志文章

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