The role of the sarcoplasmic reticulum in the response of isolated ferret cardiac muscle to beta‐adrenergic stimulation

Abstract

SUMMARY,/-Adrenergic stimulation of cardiac muscle leads to an increase in the strength of contraction and an abbreviation of its time course. We have investigated the role of the sarcoplasmic reticulum in these changes by monitoring force and cytoplasmic [Ca2+] in ferret papillary muscles, and the Ca2+ current in isolated ferret myocytes, during the application of isoprenaline in the absence and presence of the sarcoplasmic reticulum inhibitor ryanodine (10-6 mol/l). Isoprenaline (10-6 mol/l) led to a marked increase in the size of both the twitch and Ca2+ transient, and a decrease in their duration. In the presence of ryanodine, application of isoprenaline had no significant effect on either the size or the time course of the twitch. However, the increase in the Ca2+ current in response to isoprenaline was the same in the absence and presence of ryanodine. Increasing bathing [Ca2+] led to a prolongation of both the twitch and the Ca2+ transient. In the presence of ryanodine, increasing bathing [Ca2+] still increased the size, but decreased the duration, of the twitch. These data provide direct evidence that both the inotropic and lusitropic effects of isoprenaline are mediated via the sarcoplasmic reticulum.

Sarcoplasmic reticulum Ca2+ content, L‐type Ca2+ current and the Ca2+ transient in rat myocytes during β‐adrenergic Stimulation

“…The present data show that the abbreviation of the Ca 2+ transient that occurs during β‐adrenergic stimulation is not altered when the period of depolarization is kept constant, in agreement with the work of Morad & Rolett (1972); this argues against a significant role for changes in action potential duration in this abbreviation. The abbreviation of the Ca 2+ transient is, however, abolished by the SR Ca 2+ release channel inhibitor ryanodine (Shah et al 1994) and the SR Ca 2+ ‐ATPase inhibitor thapsigargin (this study), suggesting an important role for the SR in the abbreviation. Isoprenaline had no effect on the time course of the Ca 2+ transient or contraction in the presence of an antibody against phospholamban (Sham et al 1991) or in mice which do not express phospholamban (Luo et al 1994).…”

“…The present data show that the increase in the amplitude of the Ca 2+ transient that occurred during β stimulation was not significantly altered when the period of depolarization was kept constant (Figs 1 and 2), suggesting that changes in action potential configuration are not the only determinant of the changes in the Ca 2+ transient observed during β‐adrenergic stimulation. However, inhibition of the SR Ca 2+ release channel by ryanodine (Shah, Than, White, Bennett & Orchard, 1994) or the SR Ca 2+ ‐ATPase by thapsigargin (Fig. 11) inhibited the increase in the amplitude of the Ca 2+ transient during β stimulation; this suggests that the increase in the size of the transient is due to increased Ca 2+ release from the SR during such stimulation.…”

Fatty acids are important for the Frank–Starling mechanism and Gregg effect but not for catecholamine response in isolated rat hearts

“…1980, Pepe et al . 1999) by promoting calcium entry into the cell and then into the mitochondria (Shah et al . 1994, Pepe et al .…”

“…1999). The increased cytosolic calcium is responsible for the augmented force of contraction, while mitochondrial calcium activates pyruvate phosphatase, which mediates PDC activation by dephosphorylation (Shah et al . 1994, Pepe et al .…”

The Effect of Acute Ethanol Exposure on the Chronotropic and Inotropic Function of the Rat Right Atrium

“…The concentration of ISO that produced this rate of 333 beats min À1 is also the approximate concentration that produces the maximum active tension development. The positive inotropic response to ISO was probably not blunted by a rate-induced increase in passive tension because b 1 -receptor stimulation enhances Ca 2 uptake by the sarcoplasmic reticulum, in addition to its effect on Ca 2 in¯ux through the sarcolemma (Shah et al 1994).…”