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

Abstract

â-Adrenergic stimulation increases the force of contraction and the rate of relaxation of cardiac muscle. These changes appear to be due to an increase in the amplitude, and abbreviation, of the Ca¥ transient that initiates contraction. The precise mechanisms responsible for these changes in the Ca¥ transient are unclear, although it is known that â_agonists stimulate adenylate cyclase, thus increasing cAMP within the cell and activating cAMP-dependent protein kinase (PKA). There are a number of subsequent changes in the excitation-contraction coupling pathway which could bring about the â-adrenergic-induced changes in the Ca¥ transient. (i) â_Adrenergic stimulation alters action potential duration, although the effect is variable; action potential duration has been reported to increase, stay the same, or decrease (Tsien, Journal of Physiology (1997) (10 mmol l¢) was used to elicit Ca¥ release from the sarcoplasmic reticulum (SR). Isoprenaline increased the integral of the subsequent rise in cytoplasmic [Ca¥] to 175 ± 13 % of control. 5. Abbreviation of conditioning pulse duration in the presence of isoprenaline was used to reduce the amplitude of the Ca¥ transient to control levels. Under these conditions, the amplitude of the Ca¥ transient was again graded with the amplitude of ICa in the same way as under control conditions. 6. Nifedipine (2 ìmol l¢) was also used to decrease Ca¥ transient amplitude in the presence of isoprenaline. In the presence of isoprenaline and nifedipine, the amplitude of the Ca¥ transient again showed a bell-shaped voltage dependence. 7. The SR Ca¥-ATPase inhibitor thapsigargin (2·5 ìmol l¢) reduced the effect of isoprenaline on the amplitude of the Ca¥ transient. In the presence of thapsigargin, the size of the Ca¥ transient increased as ICa increased in response to isoprenaline. 8. These data suggest that the increase in the amplitude of the Ca¥ transient produced by â_adrenergic stimulation in cardiac muscle is due to an increase in the gain of the SR Ca¥ release process, due principally to an increase in the Ca¥ content of the SR.

Arrhythmias, elicited by catecholamines and serotonin, vanish in human chronic atrial fibrillation

“…This finding is inconsistent with the idea of leaky sarcoplasmic reticulum in AF. The agonists must have produced an additional Ca 2+ load, as has been reported under βAR stimulation (21). The increased Ca 2+ load facilitates the release process (22), consistent with the increased CaTs observed with 5-HT, FSK, and ISO in cardiomyocytes from patients with SR. βAR stimulation increases the Ca 2+ sensitivity of the RyR2 channels and reportedly increases the likelihood of RyR2 clusters opening and triggering release from neighboring clusters 22).…”

β-Adrenergic Stimulation Synchronizes Intracellular Ca 2+ Release During Excitation-Contraction Coupling in Cardiac Myocytes

“…16 This discrepancy might be attributable to the inclusion of EGTA in our experiments. Alternatively, it could be the result of different stimulation/ conditioning protocols used, because in the present study cells were electrically stimulated at a low frequency (10-to 15-second intervals), whereas in most previous studies cells were paced at higher frequencies or primed by conditioning pulses.…”

Increasing Ryanodine Receptor Open Probability Alone Does Not Produce Arrhythmogenic Calcium Waves

“…24 In addition isoproterenol can increase SR Ca 2ϩ content. 25,26 We therefore hypothesized that caffeine in isolation reduces both SR Ca 2ϩ content and threshold for waves, so the SR content falls below the threshold for Ca 2ϩ waves. Isoproterenol may therefore act by increasing the SR Ca 2ϩ content above the threshold.…”