Role of intracellular calcium handling in force-interval relationships of human ventricular myocardium.

Abstract

Experiments were performed in human working myocardium to investigate the relationship of intracellular calcium handling and availability to alterations in the strength of contraction produced by changes in stimulation rate and pattern. Both control and myopathic muscles exhibited potentiation of peak isometric force during the postextrasystolic contraction which was associated with an increase in the peak intracellular calcium transient. Frequency-related force potentiation was attenuated in myopathic muscles compared to controls. This occurred despite an increase in resting intracellular calcium and in the peak amplitude of the calcium transient as detected with aequorin. Therefore, abnormalities in contractile function of myopathic muscles during frequency-related force potentiation are not due to decreased availability of intracellular calcium, but more likely reflect differences in myofibrillar calcium responsiveness. Sarcolemmal calcium influx may also contribute to frequency-related changes in contractile force in myopathic muscles as suggested by a decrease in action potential duration with increasing stimulation frequency which is associated with fluctuations in peak calcium transient amplitude. (J.

Sphingosine 1-Phosphate Receptor-1 Enhances Mitochondrial Function and Reduces Cisplatin-Induced Tubule Injury

“…This is consistent with a protective phenotype, as similar ultrastructural analyses show that mitochondria are elongated in PTs of control mice but are fragmented after IRI 26 ; mitochondrial fragmentation contributes to disruption of mitochondrial function and eventually cell death in AKI. 42 The observed increases in mitochondrial gene expression, such as those important for fission and fusion, and in basal mitochondrial respiration rate in cells overexpressing S1P1 support the concept that S1P1 play a role in mitochondrial stabilization. In addition, increased PGC-1a expression in these cells (data not shown) is consistent with increased mitochondrial biogenesis and the removal of reactive oxygen species to preserve cell function.…”

Determinants of frequency-dependent contraction and relaxation of mammalian myocardium

“…Second, and less well understood, is that the processes underlying frequency dependent behavior are geared to provide an increase in contractility, and thus may impact on the temporal resolution via which PRP is achieved. Further evidence in that PRP and FFR are closely linked is found in the studies on failing myocardium, where both PRP [53] and FFR [3,54] seem to be blunted and hallmarks of the contractile phenotype of failing myocardium.…”

“…This important regulatory mechanism was first described in the year 1871; Henry Bowditch noted that the contractile force of the frog heart increased when it was paced at increasing frequency [1]. Since the first description of this force frequency relationship (FFR), the underlying mechanism has been a target for experimental investigation [2][3][4][5][6][7]. Although several contributing factors and modifiers of the FFR have been identified, our current understanding of frequency dependent activation is far from complete.…”

Effect of inotropic stimulation on the negative force-frequency relationship in the failing human heart.

“…Following interventions that excessively increase intracellular Ca2 , such as high extracellular Ca2 , an increase in stimulation frequency in human muscle strip preparations causes an abbreviation of action potential duration (APD) accompanied by a decreased augmentation of tension. 4 In addition, at higher stimulation rates, the Ca2' sensitivity of myofilaments in myopathic …”