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Updated: Sep 19, 2026
Optical Mapping of Intra-Sarcoplasmic Reticulum Ca2+ and Transmembrane Potential in the Langendorff-perfused Rabbit Heart
Published on: September 10, 2015
Modulation of cardiac Ca2+ channels by isoproterenol studied in transgenic mice with altered SR Ca2+ content
H Sako1, S A Green, E G Kranias
1Department of Pharmacology and Cell Biophysics, University of Cincinnati College of Medicine, Ohio 45267, USA.
Abstract:
Phospholamban (PLB) ablation is associated with enhanced sarcoplasmic reticulum (SR) Ca2+ uptake and attenuation of the cardiac contractile responses to beta-adrenergic agonists. In the present study, we compared the effects of isoproterenol (Iso) on the Ca2+ currents (ICa) of ventricular myocytes isolated from wild-type (WT) and PLB knockout (PLB-KO) mice. Current density and voltage dependence of ICa were similar between WT and PLB-KO cells. However, ICa recorded from PLB-KO myocytes had significantly faster decay kinetics. Iso increased ICa amplitude in both groups in a dose-dependent manner (50% effective concentration, 57.1 nM). Iso did not alter the rate of ICa inactivation in WT cells but significantly prolonged the rate of inactivation in PLB-KO cells. When Ba2+ was used as the charge carrier, Iso slowed the decay of the current in both WT and PLB-KO cells. Depletion of SR Ca2+ by ryanodine also slowed the rate of inactivation of ICa, and subsequent application of Iso further reduced the inactivation rate of both groups. These results suggest that enhanced Ca2+ release from the SR offsets the slowing effects of beta-adrenergic receptor stimulation on the rate of inactivation of ICa.
Insights
Phospholamban (PLB) knockout mice exhibit faster calcium current decay. Beta-adrenergic stimulation affects calcium handling differently in these mice, suggesting altered SR calcium release.
Area of Science:
- Cardiovascular Physiology
- Molecular Cardiology
- Calcium Signaling
Background:
- Phospholamban (PLB) ablation impacts sarcoplasmic reticulum (SR) Ca2+ uptake and beta-adrenergic responses.
- Understanding the role of PLB in regulating cardiac calcium currents is crucial for cardiac function.
Purpose of the Study:
- To compare the effects of isoproterenol (Iso) on Ca2+ currents (ICa) in ventricular myocytes from wild-type (WT) and PLB knockout (PLB-KO) mice.
- To investigate the influence of PLB on the kinetics and modulation of cardiac Ca2+ currents.
Main Methods:
- Electrophysiological recordings of Ca2+ currents (ICa) in isolated ventricular myocytes from WT and PLB-KO mice.
- Application of isoproterenol (Iso) to assess dose-dependent effects on ICa.
- Utilized Ba2+ as a charge carrier and ryanodine to deplete SR Ca2+ to probe mechanisms.
Main Results:
- PLB-KO myocytes showed significantly faster ICa decay kinetics compared to WT.
- Iso increased ICa amplitude similarly in both groups but differentially affected inactivation rates.
- Enhanced SR Ca2+ release in PLB-KO cells appears to offset beta-adrenergic effects on ICa inactivation.
Conclusions:
- PLB deficiency alters cardiac Ca2+ current decay kinetics and response to beta-adrenergic stimulation.
- Enhanced SR Ca2+ release in PLB-KO hearts plays a significant role in modulating Ca2+ current dynamics.
- These findings provide insights into the complex regulation of cardiac calcium handling by PLB.
