Dynamical effects of calcium-sensitive potassium currents on voltage and calcium alternans

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Key points: A mathematical model of a small conductance Ca2 +-activated potassium (SK) channel was developed and incorporated into a physiologically detailed ventricular myocyte model. Ca2+-sensitive K+ currents promote negative intracellular Ca2+ to membrane voltage (CAi 2+→ Vm) coupling. Increase of Ca2+-sensitive K+ currents can be responsible for electromechanically discordant alternans and quasiperiodic oscillations at the cellular level. At the tissue level, Turing-type instability can occur when Ca2+-sensitive K+ currents are increased. Abstract: Cardiac alternans is a precursor to life-threatening arrhythmias. Alternans can be caused by instability of the membrane voltage (Vm), instability of the intracellular Ca2+ ((Formula presented.)) cycling, or both. Vm dynamics and (Formula presented.) dynamics are coupled via Ca2+-sensitive currents. In cardiac myocytes, there are several Ca2+-sensitive potassium (K+) currents such as the slowly activating delayed rectifier current (IKs) and the small conductance Ca2+-activated potassium (SK) current (ISK). However, the role of these currents in the development of arrhythmias is not well understood. In this study, we investigated how these currents affect voltage and Ca2+ alternans using a physiologically detailed computational model of the ventricular myocyte and mathematical analysis. We define the coupling between Vm and (Formula presented.) cycling dynamics ((Formula presented.) →Vm coupling) as positive (negative) when a larger Ca2+ transient at a given beat prolongs (shortens) the action potential duration (APD) of that beat. While positive coupling predominates at baseline, increasing IKs and ISK promote negative (Formula presented.) →Vm coupling at the cellular level. Specifically, when alternans is Ca2+-driven, electromechanically (APD–Ca2+) concordant alternans becomes electromechanically discordant alternans as IKs or ISK increase. These cellular level dynamics lead to different types of spatially discordant alternans in tissue. These findings help to shed light on the underlying mechanisms of cardiac alternans especially when the relative strength of these currents becomes larger under pathological conditions or drug administrations.

Original languageEnglish (US)
Pages (from-to)2285-2297
Number of pages13
JournalJournal of Physiology
Volume595
Issue number7
DOIs
StatePublished - Apr 1 2017

Fingerprint

Muscle Cells
Cardiac Arrhythmias
Small-Conductance Calcium-Activated Potassium Channels
Potassium
Calcium
Membranes
Cardiac Myocytes
Action Potentials
Theoretical Models
Pharmaceutical Preparations

Keywords

  • cardiac alternans
  • cardiac electrophysiology
  • cardiac function
  • cardiac potassium current

ASJC Scopus subject areas

  • Physiology

Cite this

Dynamical effects of calcium-sensitive potassium currents on voltage and calcium alternans. / Kennedy, Matthew; Bers, Donald M; Chiamvimonvat, Nipavan; Sato, Daisuke.

In: Journal of Physiology, Vol. 595, No. 7, 01.04.2017, p. 2285-2297.

Research output: Contribution to journalArticle

@article{0d713b950da746428606489d71f70194,
title = "Dynamical effects of calcium-sensitive potassium currents on voltage and calcium alternans",
abstract = "Key points: A mathematical model of a small conductance Ca2 +-activated potassium (SK) channel was developed and incorporated into a physiologically detailed ventricular myocyte model. Ca2+-sensitive K+ currents promote negative intracellular Ca2+ to membrane voltage (CAi 2+→ Vm) coupling. Increase of Ca2+-sensitive K+ currents can be responsible for electromechanically discordant alternans and quasiperiodic oscillations at the cellular level. At the tissue level, Turing-type instability can occur when Ca2+-sensitive K+ currents are increased. Abstract: Cardiac alternans is a precursor to life-threatening arrhythmias. Alternans can be caused by instability of the membrane voltage (Vm), instability of the intracellular Ca2+ ((Formula presented.)) cycling, or both. Vm dynamics and (Formula presented.) dynamics are coupled via Ca2+-sensitive currents. In cardiac myocytes, there are several Ca2+-sensitive potassium (K+) currents such as the slowly activating delayed rectifier current (IKs) and the small conductance Ca2+-activated potassium (SK) current (ISK). However, the role of these currents in the development of arrhythmias is not well understood. In this study, we investigated how these currents affect voltage and Ca2+ alternans using a physiologically detailed computational model of the ventricular myocyte and mathematical analysis. We define the coupling between Vm and (Formula presented.) cycling dynamics ((Formula presented.) →Vm coupling) as positive (negative) when a larger Ca2+ transient at a given beat prolongs (shortens) the action potential duration (APD) of that beat. While positive coupling predominates at baseline, increasing IKs and ISK promote negative (Formula presented.) →Vm coupling at the cellular level. Specifically, when alternans is Ca2+-driven, electromechanically (APD–Ca2+) concordant alternans becomes electromechanically discordant alternans as IKs or ISK increase. These cellular level dynamics lead to different types of spatially discordant alternans in tissue. These findings help to shed light on the underlying mechanisms of cardiac alternans especially when the relative strength of these currents becomes larger under pathological conditions or drug administrations.",
keywords = "cardiac alternans, cardiac electrophysiology, cardiac function, cardiac potassium current",
author = "Matthew Kennedy and Bers, {Donald M} and Nipavan Chiamvimonvat and Daisuke Sato",
year = "2017",
month = "4",
day = "1",
doi = "10.1113/JP273626",
language = "English (US)",
volume = "595",
pages = "2285--2297",
journal = "Journal of Physiology",
issn = "0022-3751",
publisher = "Wiley-Blackwell",
number = "7",

}

TY - JOUR

T1 - Dynamical effects of calcium-sensitive potassium currents on voltage and calcium alternans

AU - Kennedy, Matthew

AU - Bers, Donald M

AU - Chiamvimonvat, Nipavan

AU - Sato, Daisuke

PY - 2017/4/1

Y1 - 2017/4/1

N2 - Key points: A mathematical model of a small conductance Ca2 +-activated potassium (SK) channel was developed and incorporated into a physiologically detailed ventricular myocyte model. Ca2+-sensitive K+ currents promote negative intracellular Ca2+ to membrane voltage (CAi 2+→ Vm) coupling. Increase of Ca2+-sensitive K+ currents can be responsible for electromechanically discordant alternans and quasiperiodic oscillations at the cellular level. At the tissue level, Turing-type instability can occur when Ca2+-sensitive K+ currents are increased. Abstract: Cardiac alternans is a precursor to life-threatening arrhythmias. Alternans can be caused by instability of the membrane voltage (Vm), instability of the intracellular Ca2+ ((Formula presented.)) cycling, or both. Vm dynamics and (Formula presented.) dynamics are coupled via Ca2+-sensitive currents. In cardiac myocytes, there are several Ca2+-sensitive potassium (K+) currents such as the slowly activating delayed rectifier current (IKs) and the small conductance Ca2+-activated potassium (SK) current (ISK). However, the role of these currents in the development of arrhythmias is not well understood. In this study, we investigated how these currents affect voltage and Ca2+ alternans using a physiologically detailed computational model of the ventricular myocyte and mathematical analysis. We define the coupling between Vm and (Formula presented.) cycling dynamics ((Formula presented.) →Vm coupling) as positive (negative) when a larger Ca2+ transient at a given beat prolongs (shortens) the action potential duration (APD) of that beat. While positive coupling predominates at baseline, increasing IKs and ISK promote negative (Formula presented.) →Vm coupling at the cellular level. Specifically, when alternans is Ca2+-driven, electromechanically (APD–Ca2+) concordant alternans becomes electromechanically discordant alternans as IKs or ISK increase. These cellular level dynamics lead to different types of spatially discordant alternans in tissue. These findings help to shed light on the underlying mechanisms of cardiac alternans especially when the relative strength of these currents becomes larger under pathological conditions or drug administrations.

AB - Key points: A mathematical model of a small conductance Ca2 +-activated potassium (SK) channel was developed and incorporated into a physiologically detailed ventricular myocyte model. Ca2+-sensitive K+ currents promote negative intracellular Ca2+ to membrane voltage (CAi 2+→ Vm) coupling. Increase of Ca2+-sensitive K+ currents can be responsible for electromechanically discordant alternans and quasiperiodic oscillations at the cellular level. At the tissue level, Turing-type instability can occur when Ca2+-sensitive K+ currents are increased. Abstract: Cardiac alternans is a precursor to life-threatening arrhythmias. Alternans can be caused by instability of the membrane voltage (Vm), instability of the intracellular Ca2+ ((Formula presented.)) cycling, or both. Vm dynamics and (Formula presented.) dynamics are coupled via Ca2+-sensitive currents. In cardiac myocytes, there are several Ca2+-sensitive potassium (K+) currents such as the slowly activating delayed rectifier current (IKs) and the small conductance Ca2+-activated potassium (SK) current (ISK). However, the role of these currents in the development of arrhythmias is not well understood. In this study, we investigated how these currents affect voltage and Ca2+ alternans using a physiologically detailed computational model of the ventricular myocyte and mathematical analysis. We define the coupling between Vm and (Formula presented.) cycling dynamics ((Formula presented.) →Vm coupling) as positive (negative) when a larger Ca2+ transient at a given beat prolongs (shortens) the action potential duration (APD) of that beat. While positive coupling predominates at baseline, increasing IKs and ISK promote negative (Formula presented.) →Vm coupling at the cellular level. Specifically, when alternans is Ca2+-driven, electromechanically (APD–Ca2+) concordant alternans becomes electromechanically discordant alternans as IKs or ISK increase. These cellular level dynamics lead to different types of spatially discordant alternans in tissue. These findings help to shed light on the underlying mechanisms of cardiac alternans especially when the relative strength of these currents becomes larger under pathological conditions or drug administrations.

KW - cardiac alternans

KW - cardiac electrophysiology

KW - cardiac function

KW - cardiac potassium current

UR - http://www.scopus.com/inward/record.url?scp=85016502050&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85016502050&partnerID=8YFLogxK

U2 - 10.1113/JP273626

DO - 10.1113/JP273626

M3 - Article

C2 - 27902841

AN - SCOPUS:85016502050

VL - 595

SP - 2285

EP - 2297

JO - Journal of Physiology

JF - Journal of Physiology

SN - 0022-3751

IS - 7

ER -