Isoprenaline enhances local Ca2+ release in cardiac myocytes.
OBJECTIVE
Contraction of cardiac myocytes is controlled by the generation and amplification of intracellular Ca2+ signals. The key step of this process is the coupling between sarcolemma L-type Ca2+ channels (LCCs) and ryanodine receptors (RyRs) in the sarcoplasmic reticulum (SR). Beta-adrenergic stimulation is an important regulatory mechanism for this coupling process. But the details underlied the global level, which require local Ca2+ release study are still unclear. The present study is to explore the effects of beta-adrenergic stimulation on local Ca2+ release.


METHODS
Using confocal microscopy combined with loose-seal patch-clamp approaches, effects of isoprenaline (1 micromol/L), a beta-adrenergic agonist, on local SR Ca2+ release triggered by Ca2+ influx through LCCs in intact rat cardiac myocytes were investigated.


RESULTS
Isoprenaline increased the intensity of ensemble averaged local Ca2+ transients, the peak of which displayed a typical bell-shaped voltage-dependence over the membrane voltages ranging from approximately -40 mV to approximately +35 mV. Further analysis showed that this enhancement could be explained by the increased coupling fidelity (which refers the increased probability of RyRs activation upon depolarization), and the increased amplitude of evoked Ca2+ sparks [due to more Ca2+ releases through local RyRs]. In addition, isoprenaline decreased the first latency, which displayed a typical 'U ' shaped voltage-dependence, showing the available acceleration and synchronization of beta-adrenergic stimulation on intracellular calcium release.


CONCLUSIONS
Isoprenaline enhances local Ca2+ release in cardiac myocytes. These results underscore the importance of regulation of beta-adrenergic stimulation on local intermolecular signals between LCCs and RyRs in heart cells.
Shen
Jian-xin
JX
Department of Physiology, Shantou University Medical College, Shantou 515041, China. jxshen@stu.edu.cn
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020746:Calcium Channels, L-Type / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects*; D002469:Cell Separation; D007545:Isoproterenol / Q000494:pharmacology*; D032383:Myocytes, Cardiac / Q000166:cytology / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D019837:Ryanodine Receptor Calcium Release Channel / Q000378:metabolism; D012519:Sarcoplasmic Reticulum / Q000378:metabolism
D000318:Adrenergic beta-Agonists; D020746:Calcium Channels, L-Type; D019837:Ryanodine Receptor Calcium Release Channel; D007545:Isoproterenol; D002118:Calcium