Open AccessIsoprenaline enhances local Ca 2+ release in cardiac myocytes 1
Author(s) -
SHEN Jianxin
Publication year - 2006
Publication title -
acta pharmacologica sinica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.514
H-Index - 90
eISSN - 1745-7254
pISSN - 1671-4083
DOI - 10.1111/j.1745-7254.2006.00383.x
Subject(s) - isoprenaline , ryanodine receptor , chemistry , biophysics , sarcolemma , myocyte , medicine , stimulation , depolarization , serca , agonist , endoplasmic reticulum , endocrinology , receptor , biology , biochemistry , atpase , enzyme
Aim: Contraction of cardiac myocytes is controlled by the generation and amplification of intracellular Ca 2+ signals. The key step of this process is the coupling between sarcolemma L‐type Ca 2+ channels (LCCs) and ryanodine receptors (RyRs) in the sarcoplasmic reticulum (SR). β‐Adrenergic stimulation is an important regulatory mechanism for this coupling process. But the details underlied the global level, which require local Ca 2+ release study are still unclear. The present study is to explore the effects of β‐adrenergic stimulation on local Ca 2+ release. Methods : Using confocal microscopy combined with loose‐seal patch‐clamp approaches, effects of isoprenaline (1 μmol‐L −1 ), a β‐adrenergic agonist, on local SR Ca 2+ release triggered by Ca 2+ influx through LCCs in intact rat cardiac myocytes were investigated. Results : Isoprenaline increased the intensity of ensemble averaged local Ca 2+ transients, the peak of which displayed a typical bell‐shaped voltage‐dependence over the membrane voltages ranging from ∼‐40mV to ∼+35mV. 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 Ca 2+ sparks (due to more Ca 2+ 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 β‐adrenergic stimulation on intracellular calcium release. Conclusions : Isoprenaline enhances local Ca 2+ release in cardiac myocytes. These results underscore the importance of regulation of β‐adrenergic stimulation on local intermolecular signals between LCCs and RyRs in heart cells.