Differential lusitropic responsiveness to β-adrenergic stimulation in rat atrial and ventricular cardiac myocytes

Abstract

Cardiac myocyte relaxation is brought about mainly through Ca2+ uptake into the sarcoplasmic reticulum (SR) by a Ca2+-ATPase isoform, SERCA2a. Its activity is modulated by another protein, phospholamban (PLB). The levels of both proteins differ in some mammals between atrial and ventricular myocardium and this may lead to differences in relaxation, especially under stimulatory conditions. At a concentration of 100 nM, the beta-adrenergic agonist isoprenaline (ISO) accelerates the relaxation of rat papillary muscle more than that of the left atria (16.4 versus 4.0% hastening of time to 50% relaxation, respectively). Ventricular myocytes were 24.7% quicker in reaching 50% of their diastolic length after contraction when treated with ISO compared to atrial myocytes, which were only 3.6% faster. Ca2+ fluorescence transients were also abbreviated in ventricular compared to atrial myocytes exposed to ISO (41.9 versus 25.2% hastening of time to 50% peak Ca2+ respectively). Ca2+ uptake into ventricular SR vesicles was increased by 13% in the presence of protein kinase A while that into atrial SR vesicles remained unaffected. Western blotting analysis revealed 23% less SERCA2a protein, but 76% more PLB in ventricular compared to atrial tissue. We conclude that the distinct levels of SERCA2a and PLB in ventricular and atrial myocardium are responsible for the differential modulation of the relaxation process arising from beta-adrenergic stimulation in single rat atrial and ventricular myocytes.

Phospholamban and cardiac function: a comparative perspective in vertebrates

“…As shown in both human and murine heart, atrial cells express a lower content of PLN with respect to the ventricle and possess a lower PLN/SERCA2a ratio (Koss et al 1995, Bokník et al 1999, Freestone et al 2000. As shown in both human and murine heart, atrial cells express a lower content of PLN with respect to the ventricle and possess a lower PLN/SERCA2a ratio (Koss et al 1995, Bokník et al 1999, Freestone et al 2000.…”

Fractalkine in human inflammatory cardiomyopathy

“…At culture day 3, the spontaneous contraction rate was monitored at 25°C in the absence and presence of 0.5–50 nM isoproterenol without and with 2.5 ng/ml CX3CL1 using an inverse phase contrast microscope (Olympus IMT-2, Olympus, Hamburg, Germany) equipped with a video camera linked to a computer via a pinnacle studio TM MovieBox. Monitoring of the spontaneous contraction rate was performed 30 s after addition of the respective substance solutions 16 17…”

Crucial role of the sarcoplasmic reticulum in the developmental regulation of Ca2+transients and contraction in cardiomyocytes derived from embryonic stem cells

“…The RyR2 +/+ and RyR2 −/− ESCMs, however, did not show variations among the subtypes after differentiation (data not shown), making comparisons among the cell populations possible. Furthermore, the difference in the dynamics of Ca 2+ transients and contraction between atrial and ventricular cardiomyocytes are minor (30) and cannot explain the great alterations in the dynamics of cardiac Ca 2+ transients seen in the RyR2 −/− ESCMs. These findings, therefore, lead us to conclude that SR Ca 2+ release via a functional RyR2 is essential not only to the increase in beating rate of ESCMs (16), but also to the rapid upstroke and reduced time‐to‐peak of Ca 2+ transients and contractile function at early, intermediate, and late cardiomyocyte differentiation stages.…”