Mechanical stretch increases intracellular calcium concentration in cultured ventricular cells from neonatal rats

Abstract

We investigated the effects of mechanical stretch on intracellular calcium concentration ([Ca2+]i) of cultured neonatal rat ventricular cells using microfluorometry with fura-2. Myocytes were cultured on laminin-coated silicon rubber and stretched by pulling the rubber with a manipulator. Myocytes were either mildly stretched (to less than 11.5% of control length), moderately so (to 115%-125% of control length), or extensively (to over 125% of the control length). "Quick stretches" (accomplished within 10s) of moderate to extensive intensities produced a large transient increase of [Ca2+]i in the early phase of stretch (30 s-2 min), followed by a small but sustained increase during the late phase of stretch (5-10 min). The initial transient increase in [Ca2+]i after the "quick stretch" was preserved in the presence of gallopamil (10(-7) M) or ryanodine (10(-5) M), but was absent in Ca(2+)-free medium or in the presence of gadolinium (10(-7) M). The late or steady state [Ca2+]i increase was observed in the presence of gadolinium, gallopamil, or ryanodine but was abolished in Ca(2+)-free medium. A steady-state increase in [Ca2+]i was also evoked by "slow stretch" in which cells were slowly pulled to the final length within 1-2 min. As the presence of external Ca2+ was indispensable, increased trans-sarcolemmal Ca2+ influx appears to be involved in both initial and steady-state increases in [Ca2+]i. The initial increase in [Ca2+]i after the "quick stretch" can be attributed to the activation of gadolinium-sensitive, stretch-activated channels.

Structural Heterogeneity in the Ventricular Wall Plays a Significant Role in the Initiation of Stretch-Induced Arrhythmias in Perfused Rabbit Right Ventricular Tissues and Whole Heart Preparations

“…Furthermore, some previous studies reported that an acute stretch can also trigger a Ca 2ϩ release from the sarcoplasmic reticulum through ryanodine receptors. 31,32 In our experiments, however, the stretch-induced excitations were still observed after administration of ryanodine. Moreover, changes in the extracellular calcium concentration did not affect the stretch-induced excitability.…”

Increased coronary perfusion augments cardiac contractility in the rat through stretch-activated ion channels

“…Cardiac myocytes exhibit activation of SACs, which is inhibited by Gd 3ϩ (24,37,40). Activation of SACs in heart cells can lead to changes in fluxes of Ca 2ϩ , Na ϩ , or K ϩ cations (7,8,35,37,39,40), which may affect the myocardial contractile state.…”

“…Filling of the coronary vessels will change hoop (circumferential) stress in the vessel wall, thereby mechanically deforming the membranes of myocardial cells. Mechanical deformation of cardiomyocytes activates stretch-activated ion channels (SACs) (24,27,28,37,39,40), thereby conducting Ca 2ϩ , Na ϩ , or K ϩ cations (7,8,35,37,39,40), which may affect the contractile state of the myocardium. Besides hoop stress, a change in perfusion will change also shear stress and may thereby induce endothelium-dependent nitric oxide (NO) release.…”

Coronary perfusion and muscle lengthening increase cardiac contraction: different stretch-triggered mechanisms

“…The second phase, the slow force response, seems to result from a slow rise in [Ca 2ϩ ] i , supporting the data reported by Allen and Kurihara (3). Stretching of isolated single cardiomyocytes led to an increase in [Ca 2ϩ ] i via SACs in the guinea pig (11), chick (40), and neonatal rat (42). Because the increase of [Ca 2ϩ ] i to myocardial stretch occurred during systole and not diastole, the involvement of SACs in the slow force response in muscle preparations was criticized by Kentish and Wrzosek (26) (23); and 4) the time course of the increase of peak [Ca 2ϩ ] i is too slow to be caused by activation of stretch-induced inward cation currents via SACs, which are normally activated within 10 ms in rat ventricular myocytes (9,45).…”