Sarcoplasmic reticulum Ca2+ content, L-type Ca2+ current and the Ca2+ transient in rat myocytes during β-adrenergic stimulation
Sarcoplasmic reticulum Ca2+ content, L-type Ca2+ current and the Ca2+ transient in rat myocytes during β-adrenergic stimulation
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DOI：
10.1111/j.1469-7793.1997.385bb.x
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发表时间：
1997-12-01
影响因子：
5.5
通讯作者：
Orchard, CH
中科院分区：
文献类型：
--
作者：
Hussain, M;Orchard, CH
1. 在从大鼠心脏分离的心室肌细胞中研究了β-肾上腺素能刺激对细胞内Ca2+瞬变和L型Ca2+电流(I-Ca)幅度之间关系的影响。在场刺激期间使用fura-2监测细胞内[Ca2+]，同时使用电压钳技术控制膜电位。2．异丙肾上腺素(1.0 μmol l(-1))产生的Ca2+瞬变幅度的增加和下降率在产生动作电位的肌细胞和用恒定持续时间和幅度的脉冲钳制的细胞中没有显着差异。3．在控制条件下，I-Ca 的电流-电压 (I-V) 关系呈钟形。 Ca2+瞬变的幅度也表现出钟形电压依赖性。在存在异丙肾上腺素的情况下，I-Ca 和 Ca2+ 瞬变的幅度在所有测试电位下都较大，并且 I-V 关系保持其钟形电压依赖性。然而，Ca2+瞬变的大小不再随着I-Ca幅度的变化而分级：小的I-Ca现在可以引起最大的Ca2+瞬变。4．快速应用咖啡因（10 mmol l(-1)）来诱导肌浆网（SR）释放Ca2+。异丙肾上腺素使细胞质 [Ca2+] 随后升高的积分增加至对照的 175 +/- 13 %。5．在存在异丙肾上腺素的情况下，调节脉冲持续时间的缩写用于降低 Ca2+ 瞬变的幅度。来控制水平。在这些条件下，Ca2+瞬变的幅度再次与I-Ca的幅度分级，其方式与对照条件下相同。6．硝苯地平 (2 mu mol l(-1)) 也可用于降低异丙肾上腺素存在下的 Ca2+ 瞬态振幅。在异丙肾上腺素和硝苯地平存在下，Ca2+瞬变幅度再次表现出钟形电压依赖性。7． SR Ca2+-ATP酶抑制剂thapsigargin (2.5 mu mol l(-1))降低了异丙肾上腺素对Ca2+瞬变幅度的影响。在毒胡萝卜素存在的情况下，Ca2+瞬变的大小随着异丙肾上腺素反应而增加的I-Ca增加而增加。8．这些数据表明，心肌中β-肾上腺素能刺激产生的Ca2+瞬变幅度的增加是由于SR Ca2+释放过程增益的增加，这主要是由于SR的Ca2+含量的增加。
1. The effect of beta-adrenergic stimulation on the relationship between the intracellular Ca2+ transient and the amplitude of the L-type Ca2+ current (I-Ca) has been investigated in ventricular myocytes isolated from rat hearts. Intracellular [Ca2+] was monitored using fura-2 during field stimulation and while membrane potential was controlled using voltage clamp techniques.2. The increase in the amplitude, and the rate of decline, of the Ca2+ transient produced by isoprenaline (1.0 mu mol l(-1)) was not significantly different in myocytes generating action potentials and in those voltage clamped with pulses of constant duration and amplitude.3. Under control conditions, the current-voltage (I-V) relationship for I-Ca was bell shaped. The amplitude of the Ca2+ transient also showed a bell-shaped voltage dependence. In the presence of isoprenaline, the amplitude of both I-Ca and the Ca2+ transient was greater at all test potentials and the I-V relationship maintained its bell-shaped voltage dependence. However, the size of the Ca2+ transient was no longer graded with changes in the amplitude of I-Ca: a small I-Ca could now elicit a maximal Ca2+ transient.4. Rapid application of caffeine (10 mmol l(-1)) was used to elicit Ca2+ release from the sarcoplasmic reticulum (SR). Isoprenaline increased the integral of the subsequent rise in cytoplasmic [Ca2+] to 175 +/- 13 % of control.5. Abbreviation of conditioning pulse duration in the presence of isoprenaline was used to reduce the amplitude of the Ca2+ transient. to control levels. Under these conditions, the amplitude of the Ca2+ transient was again graded with the amplitude of I-Ca in the same way as under control conditions.6. Nifedipine (2 mu mol l(-1)) was also used to decrease Ca2+ transient amplitude in the presence of isoprenaline. In the presence of isoprenaline and nifedipine, the amplitude of the Ca2+ transient again showed a bell-shaped voltage dependence.7. The SR Ca2+-ATPase inhibitor thapsigargin (2.5 mu mol l(-1)) reduced the effect of isoprenaline on the amplitude of the Ca2+ transient. In the presence of thapsigargin, the size of the Ca2+ transient increased as I-Ca increased in response to isoprenaline.8. These data suggest that the increase in the amplitude of the Ca2+ transient produced by beta-adrenergic stimulation in cardiac muscle is due to an increase in the gain of the SR Ca2+ release process, due principally to an increase in the Ca2+ content of the SR.