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Functional coupling between glycolysis and excitation—contraction coupling underlies alternans in cat heart cells
Author(s) -
Hüser Jörg,
Wang Yong Gao,
Sheehan Katherine A.,
Cifuentes Fredy,
Lipsius Stephen L.,
Blatter Lothar A.
Publication year - 2000
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1111/j.1469-7793.2000.00795.x
Subject(s) - myocyte , contraction (grammar) , coupling (piping) , biophysics , medicine , isoprenaline , endoplasmic reticulum , membrane potential , depolarization , chemistry , intracellular , stimulation , biology , materials science , biochemistry , metallurgy
1 Electromechanical alternans was characterized in single cat atrial and ventricular myocytes by simultaneous measurements of action potentials, membrane current, cell shortening and changes in intracellular Ca 2+ concentration ([Ca 2+ ] i ). 2 Using laser scanning confocal fluorescence microscopy, alternans of electrically evoked [Ca 2+ ] i transients revealed marked differences between atrial and ventricular myocytes. In ventricular myocytes, electrically evoked [Ca 2+ ] i transients during alternans were spatially homogeneous. In atrial cells Ca 2+ release started at subsarcolemmal peripheral regions and subsequently spread toward the centre of the myocyte. In contrast to ventricular myocytes, in atrial cells propagation of Ca 2+ release from the sarcoplasmic reticulum (SR) during the small‐amplitude [Ca 2+ ] i transient was incomplete, leading to failures of excitation‐contraction (EC) coupling in central regions of the cell. 3 The mechanism underlying alternans was explored by evaluating the trigger signal for SR Ca 2+ release (voltage‐gated L‐type Ca 2+ current, I Ca, L ) and SR Ca 2+ load during alternans. Voltage‐clamp experiments revealed that peak I Ca, L was not affected during alternans when measured simultaneously with changes of cell shortening. The SR Ca 2+ content, evaluated by application of caffeine pulses, was identical following the small‐amplitude and the large‐amplitude [Ca 2+ ] i transient. These results suggest that the primary mechanism responsible for cardiac alternans does not reside in the trigger signal for Ca 2+ release and SR Ca 2+ load. 4 β‐Adrenergic stimulation with isoproterenol (isoprenaline) reversed electromechanical alternans, suggesting that under conditions of positive cardiac inotropy and enhanced efficiency of EC coupling alternans is less likely to occur. 5 The occurrence of electromechanical alternans could be elicited by impairment of glycolysis. Inhibition of glycolytic flux by application of pyruvate, iodoacetate or β‐hydroxybutyrate induced electromechanical and [Ca 2+ ] i transient alternans in both atrial and ventricular myocytes. 6 The data support the conclusion that in cardiac myocytes alternans is the result of periodic alterations in the gain of EC coupling, i.e. the efficacy of a given trigger signal to release Ca 2+ from the SR. It is suggested that the efficiency of EC coupling is locally controlled in the microenvironment of the SR Ca 2+ release sites by mechanisms utilizing ATP, produced by glycolytic enzymes closely associated with the release channel.