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Updated: Aug 30, 2026
Isolation of Human Atrial Myocytes for Simultaneous Measurements of Ca2+ Transients and Membrane Currents
Published on: July 3, 2013
Intracellular calcium handling heterogeneities in intact guinea pig hearts
Rodolphe P Katra1, Etienne Pruvot, Kenneth R Laurita
1Heart and Vascular Research Center, Department of Biomedical Engineering, MetroHealth Campus, Case Western Reserve University, 2500 MetroHealth Dr., Rammelkamp 654, Cleveland, OH 44109-1198, USA.
Insights
Intracellular calcium handling differs significantly between the base and apex of the intact heart. These calcium handling heterogeneities may contribute to heart rhythm abnormalities.
Area of Science:
- Cardiovascular Physiology
- Cardiac Electrophysiology
- Calcium Signaling
Background:
- Regional differences in ventricular repolarization and their link to arrhythmogenesis are well-studied.
- Knowledge gaps exist regarding regional heterogeneities in intracellular calcium handling within the intact heart.
- Base-to-apex variations in cardiac repolarization and contractility suggest potential spatial differences in calcium handling.
Purpose of the Study:
- To investigate base-to-apex heterogeneities in intracellular calcium handling in the intact heart.
- To test the hypothesis that calcium handling varies spatially from the base to the apex of the ventricle.
- To assess the role of these heterogeneities in cardiac function and potential arrhythmogenesis.
Main Methods:
- Development of a novel ratiometric optical mapping system for simultaneous dual-wavelength calcium fluorescence measurement.
- Utilized intact Langendorff-perfused guinea pig hearts for experimental recordings.
- Recorded ratiometric calcium transients under normal conditions and during administration of inotropic agents (isoproterenol, verapamil).
Main Results:
- Calcium transient amplitude was significantly larger at the apex compared to the base (60% increase, P < 0.01).
- Calcium transient duration was significantly longer at the base compared to the apex (7.5% increase, P < 0.03).
- Observed base-to-apex heterogeneities in calcium handling remained consistent during pharmacological interventions affecting contractility.
Conclusions:
- Ratiometric optical mapping is a validated technique for quantifying calcium handling heterogeneities in the intact heart.
- Significant base-to-apex heterogeneities in calcium release and sequestration exist within the intact ventricle.
- These spatial variations in calcium handling correlate with known base-to-apex contractile differences and may influence arrhythmogenesis under pathological conditions.
Abstract:
Regional heterogeneities of ventricular repolarizing currents and their role in arrhythmogenesis have received much attention; however, relatively little is known regarding heterogeneities of intracellular calcium handling. Because repolarization properties and contractile function are heterogeneous from base to apex of the intact heart, we hypothesize that calcium handling is also heterogeneous from base to apex. To test this hypothesis, we developed a novel ratiometric optical mapping system capable of measuring calcium fluorescence of indo-1 at two separate wavelengths from 256 sites simultaneously. With the use of intact Langendorff-perfused guinea pig hearts, ratiometric calcium transients were recorded under normal conditions and during administration of known inotropic agents. Ratiometric calcium transients were insensitive to changes in excitation light intensity and fluorescence over time. Under control conditions, calcium transient amplitude near the apex was significantly larger (60%, P < 0.01) compared with the base. In contrast, calcium transient duration was significantly longer (7.5%, P < 0.03) near the base compared with the apex. During isoproterenol (0.05 microM) and verapamil (2.5 microM) administration, ratiometric calcium transients accurately reflected changes in contractile function, and, the direction of base-to-apex heterogeneities remained unchanged compared with control. Ratiometric optical mapping techniques can be used to accurately quantify heterogeneities of calcium handling in the intact heart. Significant heterogeneities of calcium release and sequestration exist from base to apex of the intact heart. These heterogeneities are consistent with base-to-apex heterogeneities of contraction observed in the intact heart and may play a role in arrhythmogenesis under abnormal conditions.
