Ion channel remodeling is related to intraoperative atrial effective refractory periods in patients with paroxysmal and persistent atrial fibrillation

B J Brundel, I C Van Gelder , R H Henning, R G Tieleman, A E Tuinenburg, M Wietses, J G Grandjean, W H Van Gilst , H J Crijns

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

BACKGROUND: Sustained shortening of the atrial effective refractory period (AERP), probably due to reduction in the L-type calcium current, is a major factor in the initiation and maintenance of atrial fibrillation (AF). We investigated underlying molecular changes by studying the relation between gene expression of the L-type calcium channel and potassium channels and AERP in patients with AF.

METHODS AND RESULTS: mRNA and protein expression were determined in the left and right atrial appendages of patients with paroxysmal (n=13) or persistent (n=16) AF and of 13 controls in sinus rhythm using reverse transcription polymerase chain reaction and slot-blot, respectively. The mRNA content of almost all investigated ion channel genes was reduced in persistent but not in paroxysmal AF. Protein levels for the L-type Ca(2+) channel and 5 potassium channels (Kv4.3, Kv1.5, HERG, minK, and Kir3.1) were significantly reduced in both persistent and paroxysmal AF. Furthermore, AERPs were determined intraoperatively at 5 basic cycle lengths between 250 and 600 ms. Patients with persistent and paroxysmal AF displayed significant shorter AERPs. Protein levels of all ion channels investigated correlated positively with the AERP and with the rate adaptation of AERP. Patients with reduced ion channel protein expression had a shorter AERP duration and poorer rate adaptation.

CONCLUSIONS: AF is predominantly accompanied by decreased protein contents of the L-type Ca(2+) channel and several potassium channels. Reductions in L-type Ca(2+) channel correlated with AERP and rate adaptation, and they represent a probable explanation for the electrophysiological changes during AF.

Original languageEnglish
Pages (from-to)684-90
Number of pages7
JournalCirculation
Volume103
Issue number5
Publication statusPublished - 6 Feb 2001

Cite this

Brundel, B. J., Van Gelder , I. C., Henning, R. H., Tieleman, R. G., Tuinenburg, A. E., Wietses, M., ... Crijns, H. J. (2001). Ion channel remodeling is related to intraoperative atrial effective refractory periods in patients with paroxysmal and persistent atrial fibrillation. Circulation, 103(5), 684-90.
Brundel, B J ; Van Gelder , I C ; Henning, R H ; Tieleman, R G ; Tuinenburg, A E ; Wietses, M ; Grandjean, J G ; Van Gilst , W H ; Crijns, H J. / Ion channel remodeling is related to intraoperative atrial effective refractory periods in patients with paroxysmal and persistent atrial fibrillation. In: Circulation. 2001 ; Vol. 103, No. 5. pp. 684-90.
@article{fe62fb0b6303450db2e9e21a657bba92,
title = "Ion channel remodeling is related to intraoperative atrial effective refractory periods in patients with paroxysmal and persistent atrial fibrillation",
abstract = "BACKGROUND: Sustained shortening of the atrial effective refractory period (AERP), probably due to reduction in the L-type calcium current, is a major factor in the initiation and maintenance of atrial fibrillation (AF). We investigated underlying molecular changes by studying the relation between gene expression of the L-type calcium channel and potassium channels and AERP in patients with AF.METHODS AND RESULTS: mRNA and protein expression were determined in the left and right atrial appendages of patients with paroxysmal (n=13) or persistent (n=16) AF and of 13 controls in sinus rhythm using reverse transcription polymerase chain reaction and slot-blot, respectively. The mRNA content of almost all investigated ion channel genes was reduced in persistent but not in paroxysmal AF. Protein levels for the L-type Ca(2+) channel and 5 potassium channels (Kv4.3, Kv1.5, HERG, minK, and Kir3.1) were significantly reduced in both persistent and paroxysmal AF. Furthermore, AERPs were determined intraoperatively at 5 basic cycle lengths between 250 and 600 ms. Patients with persistent and paroxysmal AF displayed significant shorter AERPs. Protein levels of all ion channels investigated correlated positively with the AERP and with the rate adaptation of AERP. Patients with reduced ion channel protein expression had a shorter AERP duration and poorer rate adaptation.CONCLUSIONS: AF is predominantly accompanied by decreased protein contents of the L-type Ca(2+) channel and several potassium channels. Reductions in L-type Ca(2+) channel correlated with AERP and rate adaptation, and they represent a probable explanation for the electrophysiological changes during AF.",
keywords = "Atrial Fibrillation/genetics, Calcium Channels, L-Type/biosynthesis, Electrophysiology, Gene Expression, Humans, Intraoperative Period, Ion Channel Gating/physiology, Middle Aged, Potassium Channels/biosynthesis, RNA, Messenger/biosynthesis",
author = "Brundel, {B J} and {Van Gelder}, {I C} and Henning, {R H} and Tieleman, {R G} and Tuinenburg, {A E} and M Wietses and Grandjean, {J G} and {Van Gilst}, {W H} and Crijns, {H J}",
year = "2001",
month = "2",
day = "6",
language = "English",
volume = "103",
pages = "684--90",
journal = "Circulation",
issn = "0009-7322",
publisher = "Lippincott Williams and Wilkins",
number = "5",

}

Brundel, BJ, Van Gelder , IC, Henning, RH, Tieleman, RG, Tuinenburg, AE, Wietses, M, Grandjean, JG, Van Gilst , WH & Crijns, HJ 2001, 'Ion channel remodeling is related to intraoperative atrial effective refractory periods in patients with paroxysmal and persistent atrial fibrillation' Circulation, vol. 103, no. 5, pp. 684-90.

Ion channel remodeling is related to intraoperative atrial effective refractory periods in patients with paroxysmal and persistent atrial fibrillation. / Brundel, B J; Van Gelder , I C; Henning, R H; Tieleman, R G; Tuinenburg, A E; Wietses, M; Grandjean, J G; Van Gilst , W H; Crijns, H J.

In: Circulation, Vol. 103, No. 5, 06.02.2001, p. 684-90.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Ion channel remodeling is related to intraoperative atrial effective refractory periods in patients with paroxysmal and persistent atrial fibrillation

AU - Brundel, B J

AU - Van Gelder , I C

AU - Henning, R H

AU - Tieleman, R G

AU - Tuinenburg, A E

AU - Wietses, M

AU - Grandjean, J G

AU - Van Gilst , W H

AU - Crijns, H J

PY - 2001/2/6

Y1 - 2001/2/6

N2 - BACKGROUND: Sustained shortening of the atrial effective refractory period (AERP), probably due to reduction in the L-type calcium current, is a major factor in the initiation and maintenance of atrial fibrillation (AF). We investigated underlying molecular changes by studying the relation between gene expression of the L-type calcium channel and potassium channels and AERP in patients with AF.METHODS AND RESULTS: mRNA and protein expression were determined in the left and right atrial appendages of patients with paroxysmal (n=13) or persistent (n=16) AF and of 13 controls in sinus rhythm using reverse transcription polymerase chain reaction and slot-blot, respectively. The mRNA content of almost all investigated ion channel genes was reduced in persistent but not in paroxysmal AF. Protein levels for the L-type Ca(2+) channel and 5 potassium channels (Kv4.3, Kv1.5, HERG, minK, and Kir3.1) were significantly reduced in both persistent and paroxysmal AF. Furthermore, AERPs were determined intraoperatively at 5 basic cycle lengths between 250 and 600 ms. Patients with persistent and paroxysmal AF displayed significant shorter AERPs. Protein levels of all ion channels investigated correlated positively with the AERP and with the rate adaptation of AERP. Patients with reduced ion channel protein expression had a shorter AERP duration and poorer rate adaptation.CONCLUSIONS: AF is predominantly accompanied by decreased protein contents of the L-type Ca(2+) channel and several potassium channels. Reductions in L-type Ca(2+) channel correlated with AERP and rate adaptation, and they represent a probable explanation for the electrophysiological changes during AF.

AB - BACKGROUND: Sustained shortening of the atrial effective refractory period (AERP), probably due to reduction in the L-type calcium current, is a major factor in the initiation and maintenance of atrial fibrillation (AF). We investigated underlying molecular changes by studying the relation between gene expression of the L-type calcium channel and potassium channels and AERP in patients with AF.METHODS AND RESULTS: mRNA and protein expression were determined in the left and right atrial appendages of patients with paroxysmal (n=13) or persistent (n=16) AF and of 13 controls in sinus rhythm using reverse transcription polymerase chain reaction and slot-blot, respectively. The mRNA content of almost all investigated ion channel genes was reduced in persistent but not in paroxysmal AF. Protein levels for the L-type Ca(2+) channel and 5 potassium channels (Kv4.3, Kv1.5, HERG, minK, and Kir3.1) were significantly reduced in both persistent and paroxysmal AF. Furthermore, AERPs were determined intraoperatively at 5 basic cycle lengths between 250 and 600 ms. Patients with persistent and paroxysmal AF displayed significant shorter AERPs. Protein levels of all ion channels investigated correlated positively with the AERP and with the rate adaptation of AERP. Patients with reduced ion channel protein expression had a shorter AERP duration and poorer rate adaptation.CONCLUSIONS: AF is predominantly accompanied by decreased protein contents of the L-type Ca(2+) channel and several potassium channels. Reductions in L-type Ca(2+) channel correlated with AERP and rate adaptation, and they represent a probable explanation for the electrophysiological changes during AF.

KW - Atrial Fibrillation/genetics

KW - Calcium Channels, L-Type/biosynthesis

KW - Electrophysiology

KW - Gene Expression

KW - Humans

KW - Intraoperative Period

KW - Ion Channel Gating/physiology

KW - Middle Aged

KW - Potassium Channels/biosynthesis

KW - RNA, Messenger/biosynthesis

M3 - Article

VL - 103

SP - 684

EP - 690

JO - Circulation

JF - Circulation

SN - 0009-7322

IS - 5

ER -