AJP - Heart Calcium Transients and Cell-Sarcomere
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Am J Physiol Heart Circ Physiol 286: H648-H656, 2004. First published October 9, 2003; doi:10.1152/ajpheart.00374.2003
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Intracellular calcium handling heterogeneities in intact guinea pig hearts

Rodolphe P. Katra, Etienne Pruvot, and Kenneth R. Laurita

The Heart and Vascular Research Center, and The Department of Biomedical Engineering, MetroHealth Campus, Case Western Reserve University, Cleveland, Ohio 44109-1198

Submitted 25 August 2003 ; accepted in final form 2 October 2003

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 µM) and verapamil (2.5 µM) 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.

optical mapping; ratiometric calcium imaging; electrophysiology; contraction



Address for reprint requests and other correspondence: K. R. Laurita, Heart and Vascular Research Center, MetroHealth Campus, Case Western Reserve Univ., 2500 MetroHealth Dr., Rammelkamp 654, Cleveland, OH 44109-1198 (klaurita{at}metrohealth.org).




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