An improved model of Ba current through L-type Ca channels including voltage- and ion-dependent inactivation

S. Morotti; Eleonora Grandi; A. Summa; Kenneth S Ginsburg; Donald M Bers; S. Severi

An improved model of Ba current through L-type Ca channels including voltage- and ion-dependent inactivation

S. Morotti, Eleonora Grandi, A. Summa, Kenneth S Ginsburg, Donald M Bers, S. Severi

Pharmacology

Research output: Chapter in Book/Report/Conference proceeding › Conference contribution

Abstract

The substitution of Ba ions for Ca has been widely used to separate voltage-dependent inactivation (VDI) from Ca-dependent inactivation (CDI) of the Ca current (I_Ca) through L-type Ca channels (LTCCs). However, a modest ion-dependent inactivation of Ba current (I_Ba) has been shown experimentally. We have incorporated the Mahajan et al. Markov model of LTCC, which describes I_Ba inactivation as VDI only, into the Shannon et al excitation-contraction coupling model. We extended the LTCC model to assess whether and how experimental I_Ba inactivation could be recapitulated by modifying CDI. Simulation results show that I_Ba inactivation measured in rabbit myocytes at physiological temperature can be recapitulated when making the Ca-dependent transition rates 10-fold less sensitive to Ba vs. Ca. Our extended LTCC model provides a more faithful representation of purely VDI during I_Ca.

Original language	English (US)
Title of host publication	Computing in Cardiology
Pages	645-648
Number of pages	4
Volume	37
State	Published - 2010
Event	Computing in Cardiology 2010, CinC 2010 - Belfast, United Kingdom Duration: Sep 26 2010 → Sep 29 2010

Other

Other	Computing in Cardiology 2010, CinC 2010
Country	United Kingdom
City	Belfast
Period	9/26/10 → 9/29/10

ASJC Scopus subject areas

Computer Science Applications
Cardiology and Cardiovascular Medicine

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title = "An improved model of Ba current through L-type Ca channels including voltage- and ion-dependent inactivation",

abstract = "The substitution of Ba ions for Ca has been widely used to separate voltage-dependent inactivation (VDI) from Ca-dependent inactivation (CDI) of the Ca current (ICa) through L-type Ca channels (LTCCs). However, a modest ion-dependent inactivation of Ba current (IBa) has been shown experimentally. We have incorporated the Mahajan et al. Markov model of LTCC, which describes IBa inactivation as VDI only, into the Shannon et al excitation-contraction coupling model. We extended the LTCC model to assess whether and how experimental IBa inactivation could be recapitulated by modifying CDI. Simulation results show that IBa inactivation measured in rabbit myocytes at physiological temperature can be recapitulated when making the Ca-dependent transition rates 10-fold less sensitive to Ba vs. Ca. Our extended LTCC model provides a more faithful representation of purely VDI during ICa.",

author = "S. Morotti and Eleonora Grandi and A. Summa and Ginsburg, {Kenneth S} and Bers, {Donald M} and S. Severi",

year = "2010",

language = "English (US)",

isbn = "9781424473182",

volume = "37",

pages = "645--648",

booktitle = "Computing in Cardiology",

note = "Computing in Cardiology 2010, CinC 2010 ; Conference date: 26-09-2010 Through 29-09-2010",

}

TY - GEN

T1 - An improved model of Ba current through L-type Ca channels including voltage- and ion-dependent inactivation

AU - Morotti, S.

AU - Grandi, Eleonora

AU - Summa, A.

AU - Ginsburg, Kenneth S

AU - Bers, Donald M

AU - Severi, S.

PY - 2010

Y1 - 2010

N2 - The substitution of Ba ions for Ca has been widely used to separate voltage-dependent inactivation (VDI) from Ca-dependent inactivation (CDI) of the Ca current (ICa) through L-type Ca channels (LTCCs). However, a modest ion-dependent inactivation of Ba current (IBa) has been shown experimentally. We have incorporated the Mahajan et al. Markov model of LTCC, which describes IBa inactivation as VDI only, into the Shannon et al excitation-contraction coupling model. We extended the LTCC model to assess whether and how experimental IBa inactivation could be recapitulated by modifying CDI. Simulation results show that IBa inactivation measured in rabbit myocytes at physiological temperature can be recapitulated when making the Ca-dependent transition rates 10-fold less sensitive to Ba vs. Ca. Our extended LTCC model provides a more faithful representation of purely VDI during ICa.

AB - The substitution of Ba ions for Ca has been widely used to separate voltage-dependent inactivation (VDI) from Ca-dependent inactivation (CDI) of the Ca current (ICa) through L-type Ca channels (LTCCs). However, a modest ion-dependent inactivation of Ba current (IBa) has been shown experimentally. We have incorporated the Mahajan et al. Markov model of LTCC, which describes IBa inactivation as VDI only, into the Shannon et al excitation-contraction coupling model. We extended the LTCC model to assess whether and how experimental IBa inactivation could be recapitulated by modifying CDI. Simulation results show that IBa inactivation measured in rabbit myocytes at physiological temperature can be recapitulated when making the Ca-dependent transition rates 10-fold less sensitive to Ba vs. Ca. Our extended LTCC model provides a more faithful representation of purely VDI during ICa.

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M3 - Conference contribution

AN - SCOPUS:79953822002

SN - 9781424473182

VL - 37

SP - 645

EP - 648

BT - Computing in Cardiology

T2 - Computing in Cardiology 2010, CinC 2010

Y2 - 26 September 2010 through 29 September 2010

ER -