Preload-induced changes in isometric tension and [Ca2+]i in rat myocardium

Abstract

Preload-induced changes of active tension and [Ca2+]i are “dissociated” in mammalian myocardium. This study aimed to describe the distinct effects of preload at low and physiological [Ca2+]o. Rat RV papillary muscles were studied in isometric conditions at 25‡C and 0.33 Hz at 1 mM (hypo-Ca group) and 2.5 mM [Ca2+]o (normal-Ca group). [Ca2+]i was monitored with fura-2/AM. Increase of preload caused a rise of active tension in hypo-Ca and normal-Ca groups whereas peak fluorescence rose significantly only at low [Ca2+]o. End-diastolic tension, end-diastolic level of fluorescence, time-to-peak tension, but not time-to-peak of Ca2+ transient, progressively increased with preload. Mechanical relaxation decelerated with preload while Ca2+ transient decay time decreased in the initial phase and increased in the late phase, resulting in a prominent “bump” configuration. The “bump” was assessed as a ratio of its area to the fluorescence trace area. It was a new finding that the preload-induced rise of this ratio was twice as large in hypo-Ca. Our results indicate that preload-induced changes in active tension and [Ca2+]i are “dissociated” in rat myocardium, with relatively higher expression at low [Ca2+]o. Ca-dependence of Ca-TnC association/dissociation kinetics is thought to be a main contributor to these preload-induced effects.

The length‐dependent activation of contraction is equally impaired in impuberal male and female rats in monocrotaline‐induced right ventricular failure

“…In the healthy myocardium, the ‘bump’ is likely to be associated with slower Ca 2+ release from troponin C (TnC) and a slower rate of cross‐bridge cycling in stretched muscle, so length‐dependent changes in the characteristics of the ‘bump’ (integral magnitude and time‐to‐peak) should be consistent with putative changes in the Ca 2+ ‐TnC interaction. A recent study found that both integral magnitude and time‐to‐peak ‘bump’ were progressively elevated with gradual stretch of right ventricular muscle isolated from healthy adult rats . Similar effects were seen in the present study.…”

“…In rat myocardium, a brief delay in Ca 2+ transient decline (referred to as a ‘bump’) is commonly observed in isometrically contracting muscle . Consistently, an increase in muscle length results in an increase in the magnitude of the ‘bump’ but the overall decline in the Ca 2+ transient from peak to rest levels remained monotonous (Fig. a).…”

Differentiating the effects of β-adrenergic stimulation and stretch on calcium and force dynamics using a novel electromechanical cardiomyocyte model

“…Finally, our results showed preload-dependent changes in force generation, with a preload-dependent response to ␤-ARS, as indicated by a minor effect of ␤-ARS on force generation at low preloads (low SL). This was also mentioned in previous experimental studies (1,22). Therefore, our results highlight the importance of the preload-dependency of contractility observed at the cellular and whole organ level (Frank-Starling law).…”