Inhibition of Ca2+ current in neonatal and adult rat ventricular myocytes by the tyrosine kinase inhibitor, genistein.
Inhibition of Ca2+ current in neonatal and adult rat ventricular myocytes by the tyrosine kinase inhibitor, genistein.
复制标题
酪氨酸激酶抑制剂金雀异黄素抑制新生和成年大鼠心室肌细胞中的 Ca2 电流。
DOI：
10.1016/s0014-2999(98)00010-7
复制
发表时间：
1998
影响因子：
5
通讯作者：
Sperelakis,N
中科院分区：
文献类型：
--
作者：
Katsube,Y;Yokoshiki,H;Nguyen,L;Yamamoto,M;Sperelakis,N
横敷等人。 (Yokoshiki, H., Sumii, K., Sperelakis, N., 1996. 酪氨酸激酶抑制剂金雀异黄酮及其无活性类似物大豆黄酮对大鼠心室细胞中 L 型钙电流的抑制。 J. Mol. Cell. Cardiol. 28, 807–814) 报道金雀花黄素和大豆黄酮抑制 L 型 Ca2+电流(ICa(L)) 在幼年大鼠心室细胞中。因此，我们使用全细胞电压钳和单通道记录（细胞贴壁配置）研究了酪氨酸激酶抑制剂金雀异黄素对新鲜分离的新生儿（3-7天）和成年（2-5个月）大鼠心室肌细胞ICa(L)影响的发育差异。对于全细胞电压钳，通过从 -40 mV 的保持电位施加 300 ms 的脉冲，测量 ICa(L) 作为 +10 mV 测试电位下的峰值内向电流。为了分离 ICa(L)，移液管溶液富含 Cs+，浴液不含 Na+-、K+。 Ca2+(1.8 mM)用作电荷载体。浴液中使用 100 μM 金雀异黄素（足以达到最大效果）可使新生儿细胞的基础 ICa(L) 降低 43.3% (n=27)，使成人细胞降低 30.6% (n=14)（P<0.05）。在电流/电压关系中，峰值ICa(L)的电势在新生儿细胞中被染料木黄酮向右移动8.6 mV，在成人细胞中移动9.3 mV。金雀异黄素使新生细胞（从-16.0±3.9 mV到-26.1±4.2 mV；P<0.05）和成体细胞（-15.9±3.2 mV到-22.9±3.3 mV；P<0.05）稳态失活曲线发生偏移（向左）；斜率因子不受影响。对于细胞贴附贴片中的单通道记录，通过从 -40 mV 的保持电位到 0 mV 的测试电位施加 150 ms 脉冲来诱发 Ca2+ 电流。移液管溶液含有 110 mM Ba2+（作为电荷载体），浴液含有 150 mM K+（使静息电位接近零）。在没有 Bay K 8644 的情况下，金雀异黄素 (50 μM) 将通道的开放概率从 2.8% 降低到 0.75% (P<0.05)，在存在 Bay K 8644 的情况下，将通道的开放概率从 24% 降低到 7.9% (P<0.05)；电流的平均开放时间和斜率电导不受影响。总之，(1) 金雀异黄素抑制大鼠心室细胞中的基础 ICa(L)，(2) 金雀异黄素对未成熟细胞中 ICa(L) 的抑制作用强于成年细胞。
Yokoshiki et al. (Yokoshiki, H., Sumii, K., Sperelakis, N., 1996. Inhibition of L-type calcium current in rat ventricular cells by the tyrosine kinase inhibitor, genistein and its inactive analog, daidzein. J. Mol. Cell. Cardiol. 28, 807–814) reported that genistein and daidzein inhibited L-type Ca2+current (ICa(L)) in young rat ventricular cells. Therefore, we investigated the developmental differences in the effect of genistein, an inhibitor of tyrosine kinases, on ICa(L)in freshly-isolated neonatal (3–7 days) and adult (2–5 months) rat ventricular myocytes using whole-cell voltage clamp and single-channel recordings (cell-attached configuration). For whole-cell voltage clamp, ICa(L)was measured as the peak inward current at a test potential of +10 mV by applying a 300 ms pulse from a holding potential of −40 mV. To isolate ICa(L), the pipette solution was Cs+-rich and the bath solution was Na+-, K+-free. Ca2+(1.8 mM) was used as charge carrier. Bath application of 100 μM genistein (sufficient for maximal effect) decreased the basal ICa(L)by 43.3% (n=27) in neonatal cells and by 30.6% (n=14) in adult cells (P<0.05). In the current/voltage relationships, the potential of peak ICa(L)was shifted to the right by genistein by 8.6 mV in neonatal and by 9.3 mV in adult cells. Genistein produced a shift of the steady-state inactivation curve (to the left) in neonatal cells (from −16.0±3.9 mV to −26.1±4.2 mV; P<0.05) and in adult cells (−15.9±3.2 mV to −22.9±3.3 mV; P<0.05); the slope factor was not affected. For single-channel recordings in cell-attached patches, Ca2+currents were evoked by applying a 150 ms pulse from a holding potential of −40 mV to a test potential of 0 mV. The pipette solution contained 110 mM Ba2+(as charge carrier), and the bath solution contained 150 mM K+(to bring resting potential to near zero). Genistein (50 μM) decreased the open probability of the channels from 2.8% to 0.75% (P<0.05) in absence of Bay K 8644, and from 24% to 7.9% (P<0.05) in presence of Bay K 8644; the mean open time and the slope conductance of the currents were not affected. In conclusion, (1) genistein inhibits the basal ICa(L)in rat ventricular cells and (2) the inhibition of ICa(L)by genistein is greater in immature cells than in adult cells.
登录
查看更多内容
酪氨酸激酶抑制剂阻断血管平滑肌细胞中的钙通道电流。
DOI：
--
发表时间：
1992
期刊：
Biochemical and Biophysical Research Communications - BBRC
影响因子：
--
作者：
S. Wijetunge;Christian Aalkjaer;Michael Schachter;Alun D. Hughes
通讯作者：
Alun D. Hughes
影响因子：
64.5
作者：
MARGOLIS, B;RHEE, SG;SCHLESSINGER, J
通讯作者：
SCHLESSINGER, J
影响因子：
5
作者：
Hisashi Yokoshiki;Kotaro Sumii;Nicholas Sperelakis
通讯作者：
Hisashi Yokoshiki;Kotaro Sumii;Nicholas Sperelakis
酪氨酸激酶抑制剂金雀异黄素和 ST 638 对血管平滑肌细胞 K 电流的抑制。
影响因子：
20.1
作者：
S. Smirnov;P. Aaronson
通讯作者：
P. Aaronson
影响因子：
56.9
作者：
LEE, PL;JOHNSON, DE;WILLIAMS, LT
通讯作者：
WILLIAMS, LT