Effects of Na+/Ca2+ exchange induced by SR Ca 2+ release on action potentials and afterdepolarizations in guinea pig ventricular myocytes

C. Ian Spencer, James Sham

Research output: Contribution to journalArticle

Abstract

In cardiac cells, evoked Ca2+ releases or spontaneous Ca 2+ waves activate the inward Na+/Ca2+ exchange current (INaCa), which may modulate membrane excitability and arrhythmogenesis. In this study, we examined changes in membrane potential due to INaCa elicited by sarcoplasmic reticulum (SR) Ca2+ release in guinea pig ventricular myocytes using whole cell current clamp, fluorescence, and confocal microscopy. Inhibition of INaCa by Na +-free, Li+-containing Tyrode solution reversibly abbreviated the action potential duration at 90% repolarization (APD 90) by 50% and caused SR Ca2+ overload. APD90 was similarly abbreviated in myocytes exposed to the Na+/Ca 2+ exchange inhibitor KB-R7943 (5 μM) or after inhibition of SR Ca2+ release with ryanodine (20 μM). In the absence of extracellular Na+, spontaneous SR Ca2+ releases caused minimal changes in resting membrane potential. After the myocytes were returned to Na+-containing solution, the potentiated intracellular Ca 2+ concentration ([Ca2+]i) transients dramatically prolonged APD90 and [Ca2+]i oscillations caused delayed and early afterdepolarizations (DADs and EADs). Laser-flash photolysis of caged Ca2+ mimicked the effects of spontaneous [Ca2+]i oscillations, confirming that APD prolongation, DADs, and EADs could be ascribed to intracellular Ca2+ release. These results suggest that Na+/Ca2+ exchange is a major physiological determinant of APD and that INaCa activation by spontaneous SR Ca2+ release/oscillations, depending on the timing, can account for both DADs and EADs during SR Ca2+ overload.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume285
Issue number6 54-6
StatePublished - Dec 2003

Fingerprint

Sarcoplasmic Reticulum
Muscle Cells
Action Potentials
Guinea Pigs
pamidronate
Membrane Potentials
Ryanodine
Photolysis
Fluorescence Microscopy
Confocal Microscopy
Lasers
Membranes

Keywords

  • Ca overload
  • Delayed afterdepolarization
  • Early afterdepolarization
  • Flash photolysis
  • Ischemia-reperfusion arrhythmia
  • Sarcoplasmic reticulum
  • Triggered arrhythmia

ASJC Scopus subject areas

  • Physiology

Cite this

@article{1705844fc23d4bcea445e236f176a233,
title = "Effects of Na+/Ca2+ exchange induced by SR Ca 2+ release on action potentials and afterdepolarizations in guinea pig ventricular myocytes",
abstract = "In cardiac cells, evoked Ca2+ releases or spontaneous Ca 2+ waves activate the inward Na+/Ca2+ exchange current (INaCa), which may modulate membrane excitability and arrhythmogenesis. In this study, we examined changes in membrane potential due to INaCa elicited by sarcoplasmic reticulum (SR) Ca2+ release in guinea pig ventricular myocytes using whole cell current clamp, fluorescence, and confocal microscopy. Inhibition of INaCa by Na +-free, Li+-containing Tyrode solution reversibly abbreviated the action potential duration at 90{\%} repolarization (APD 90) by 50{\%} and caused SR Ca2+ overload. APD90 was similarly abbreviated in myocytes exposed to the Na+/Ca 2+ exchange inhibitor KB-R7943 (5 μM) or after inhibition of SR Ca2+ release with ryanodine (20 μM). In the absence of extracellular Na+, spontaneous SR Ca2+ releases caused minimal changes in resting membrane potential. After the myocytes were returned to Na+-containing solution, the potentiated intracellular Ca 2+ concentration ([Ca2+]i) transients dramatically prolonged APD90 and [Ca2+]i oscillations caused delayed and early afterdepolarizations (DADs and EADs). Laser-flash photolysis of caged Ca2+ mimicked the effects of spontaneous [Ca2+]i oscillations, confirming that APD prolongation, DADs, and EADs could be ascribed to intracellular Ca2+ release. These results suggest that Na+/Ca2+ exchange is a major physiological determinant of APD and that INaCa activation by spontaneous SR Ca2+ release/oscillations, depending on the timing, can account for both DADs and EADs during SR Ca2+ overload.",
keywords = "Ca overload, Delayed afterdepolarization, Early afterdepolarization, Flash photolysis, Ischemia-reperfusion arrhythmia, Sarcoplasmic reticulum, Triggered arrhythmia",
author = "Spencer, {C. Ian} and James Sham",
year = "2003",
month = "12",
language = "English (US)",
volume = "285",
journal = "American Journal of Physiology",
issn = "0363-6135",
publisher = "American Physiological Society",
number = "6 54-6",

}

TY - JOUR

T1 - Effects of Na+/Ca2+ exchange induced by SR Ca 2+ release on action potentials and afterdepolarizations in guinea pig ventricular myocytes

AU - Spencer, C. Ian

AU - Sham, James

PY - 2003/12

Y1 - 2003/12

N2 - In cardiac cells, evoked Ca2+ releases or spontaneous Ca 2+ waves activate the inward Na+/Ca2+ exchange current (INaCa), which may modulate membrane excitability and arrhythmogenesis. In this study, we examined changes in membrane potential due to INaCa elicited by sarcoplasmic reticulum (SR) Ca2+ release in guinea pig ventricular myocytes using whole cell current clamp, fluorescence, and confocal microscopy. Inhibition of INaCa by Na +-free, Li+-containing Tyrode solution reversibly abbreviated the action potential duration at 90% repolarization (APD 90) by 50% and caused SR Ca2+ overload. APD90 was similarly abbreviated in myocytes exposed to the Na+/Ca 2+ exchange inhibitor KB-R7943 (5 μM) or after inhibition of SR Ca2+ release with ryanodine (20 μM). In the absence of extracellular Na+, spontaneous SR Ca2+ releases caused minimal changes in resting membrane potential. After the myocytes were returned to Na+-containing solution, the potentiated intracellular Ca 2+ concentration ([Ca2+]i) transients dramatically prolonged APD90 and [Ca2+]i oscillations caused delayed and early afterdepolarizations (DADs and EADs). Laser-flash photolysis of caged Ca2+ mimicked the effects of spontaneous [Ca2+]i oscillations, confirming that APD prolongation, DADs, and EADs could be ascribed to intracellular Ca2+ release. These results suggest that Na+/Ca2+ exchange is a major physiological determinant of APD and that INaCa activation by spontaneous SR Ca2+ release/oscillations, depending on the timing, can account for both DADs and EADs during SR Ca2+ overload.

AB - In cardiac cells, evoked Ca2+ releases or spontaneous Ca 2+ waves activate the inward Na+/Ca2+ exchange current (INaCa), which may modulate membrane excitability and arrhythmogenesis. In this study, we examined changes in membrane potential due to INaCa elicited by sarcoplasmic reticulum (SR) Ca2+ release in guinea pig ventricular myocytes using whole cell current clamp, fluorescence, and confocal microscopy. Inhibition of INaCa by Na +-free, Li+-containing Tyrode solution reversibly abbreviated the action potential duration at 90% repolarization (APD 90) by 50% and caused SR Ca2+ overload. APD90 was similarly abbreviated in myocytes exposed to the Na+/Ca 2+ exchange inhibitor KB-R7943 (5 μM) or after inhibition of SR Ca2+ release with ryanodine (20 μM). In the absence of extracellular Na+, spontaneous SR Ca2+ releases caused minimal changes in resting membrane potential. After the myocytes were returned to Na+-containing solution, the potentiated intracellular Ca 2+ concentration ([Ca2+]i) transients dramatically prolonged APD90 and [Ca2+]i oscillations caused delayed and early afterdepolarizations (DADs and EADs). Laser-flash photolysis of caged Ca2+ mimicked the effects of spontaneous [Ca2+]i oscillations, confirming that APD prolongation, DADs, and EADs could be ascribed to intracellular Ca2+ release. These results suggest that Na+/Ca2+ exchange is a major physiological determinant of APD and that INaCa activation by spontaneous SR Ca2+ release/oscillations, depending on the timing, can account for both DADs and EADs during SR Ca2+ overload.

KW - Ca overload

KW - Delayed afterdepolarization

KW - Early afterdepolarization

KW - Flash photolysis

KW - Ischemia-reperfusion arrhythmia

KW - Sarcoplasmic reticulum

KW - Triggered arrhythmia

UR - http://www.scopus.com/inward/record.url?scp=0344009565&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0344009565&partnerID=8YFLogxK

M3 - Article

C2 - 12933341

AN - SCOPUS:0344009565

VL - 285

JO - American Journal of Physiology

JF - American Journal of Physiology

SN - 0363-6135

IS - 6 54-6

ER -