Ca2+ sparks are the elementary events of intracellular Ca2+ release from the sar-coplasmic reticulum in cardiac myocytes. In order to investigate whether spontaneous L-type Ca2+ channel activation contributes to the g...Ca2+ sparks are the elementary events of intracellular Ca2+ release from the sar-coplasmic reticulum in cardiac myocytes. In order to investigate whether spontaneous L-type Ca2+ channel activation contributes to the genesis of spontaneous Ca2+ sparks, we used confocal laser scanning microscopy and fluo-4 to visualize local Ca2+ sparks in intact rat ventricular myocytes. In the presence of 0.2 mmol/L CdCI2 which inhibits spontaneous L-type Ca2+ channel activation, the rate of occurrence of spontaneous Ca2+ sparks was halved from 4.20 to 2.04 events/(100 μm·s), with temporal and spatial properties of individual Ca2+ sparks unchanged. Analysis of the Cd2+-sensitive spark production revealed an open probability of-10-5 for L-type channels at the rest membrane potentials (-80 mV). Thus, infrequent and stochastic openings of sarcolemmal L-type Ca2+ channels in resting heart cells contribute significantly to the production of spontaneous Ca2+ sparks.展开更多
With a new fluorescence probe of Ca2+, STDIn-AM, 5-hydroxytryptamino (5-HT)-induced spontaneous calcium release events (calcium sparks) in cultured rat stomach fundus smooth mus-cle cells (SFSMC) are investigated by l...With a new fluorescence probe of Ca2+, STDIn-AM, 5-hydroxytryptamino (5-HT)-induced spontaneous calcium release events (calcium sparks) in cultured rat stomach fundus smooth mus-cle cells (SFSMC) are investigated by laser scanning confocal microscope. The mechanisms of initiation of Ca2+ sparks, propagating Ca2+ waves and their relation to E-C coupling are discussed. After the extracellular [Ca2+] is increased to 10 mmol/L, addition of 5-HT causes hot spots throughout the cytoplasm, which is brighter near the plasmalemma. The amplitude of the event is at least two times greater than the standard deviation of fluorescence intensity fluctuations meas-ured in the neighboring region and the duration of the Ca2+ signal is over 100 ms. The results sug-gest that 5-HT acts by the way of 5-HT2 receptors on SFSMC, then through 5-HT2 receptors cou-ples IP3/Ca2+ and DG/PKC double signal transduction pathways to cause Ca2+ release from intra-cellular Ca2+ stores and followed Ca2+ influx possibly through calcium release-activated calcium influx. The acceptor of activated 5-HT2 can also cause membrane depolarization, which then stimulates the L-type Ca2+ channels leading to Ca2+ influx. Then the local Ca2+ entry mentioned above activates ryanodine-sensitive Ca2+ release channels (RyR) on sarcoplasmic reticulum (SR) to cause local Ca2+ release events (Ca2+ sparks) through calcium-induced calcium release (CICR).展开更多
Ca2+ release through ryanodine receptors (RyRs) plays an important role in excitation-contraction coupling in heart and smooth muscle. FKBP12.6 proteins
基金supported by the National Natural Science Foundation of China(Grant No.30200088 for A-type grant)Chinese Major State Basic Research Development Program(Grant No.G2000057002).
文摘Ca2+ sparks are the elementary events of intracellular Ca2+ release from the sar-coplasmic reticulum in cardiac myocytes. In order to investigate whether spontaneous L-type Ca2+ channel activation contributes to the genesis of spontaneous Ca2+ sparks, we used confocal laser scanning microscopy and fluo-4 to visualize local Ca2+ sparks in intact rat ventricular myocytes. In the presence of 0.2 mmol/L CdCI2 which inhibits spontaneous L-type Ca2+ channel activation, the rate of occurrence of spontaneous Ca2+ sparks was halved from 4.20 to 2.04 events/(100 μm·s), with temporal and spatial properties of individual Ca2+ sparks unchanged. Analysis of the Cd2+-sensitive spark production revealed an open probability of-10-5 for L-type channels at the rest membrane potentials (-80 mV). Thus, infrequent and stochastic openings of sarcolemmal L-type Ca2+ channels in resting heart cells contribute significantly to the production of spontaneous Ca2+ sparks.
文摘With a new fluorescence probe of Ca2+, STDIn-AM, 5-hydroxytryptamino (5-HT)-induced spontaneous calcium release events (calcium sparks) in cultured rat stomach fundus smooth mus-cle cells (SFSMC) are investigated by laser scanning confocal microscope. The mechanisms of initiation of Ca2+ sparks, propagating Ca2+ waves and their relation to E-C coupling are discussed. After the extracellular [Ca2+] is increased to 10 mmol/L, addition of 5-HT causes hot spots throughout the cytoplasm, which is brighter near the plasmalemma. The amplitude of the event is at least two times greater than the standard deviation of fluorescence intensity fluctuations meas-ured in the neighboring region and the duration of the Ca2+ signal is over 100 ms. The results sug-gest that 5-HT acts by the way of 5-HT2 receptors on SFSMC, then through 5-HT2 receptors cou-ples IP3/Ca2+ and DG/PKC double signal transduction pathways to cause Ca2+ release from intra-cellular Ca2+ stores and followed Ca2+ influx possibly through calcium release-activated calcium influx. The acceptor of activated 5-HT2 can also cause membrane depolarization, which then stimulates the L-type Ca2+ channels leading to Ca2+ influx. Then the local Ca2+ entry mentioned above activates ryanodine-sensitive Ca2+ release channels (RyR) on sarcoplasmic reticulum (SR) to cause local Ca2+ release events (Ca2+ sparks) through calcium-induced calcium release (CICR).
文摘Ca2+ release through ryanodine receptors (RyRs) plays an important role in excitation-contraction coupling in heart and smooth muscle. FKBP12.6 proteins