Ichiyanagi Osamu, Ishii Kuniaki, Endoh Masao
Department of Pharmacology, Yamagata University School of Medicine, 2-2-2 Iida-nishi, 990-9585, Japan.
Pflugers Arch. 2002 May;444(1-2):107-16. doi: 10.1007/s00424-002-0808-y. Epub 2002 Mar 9.
The effects of angiotensin II (Ang II) on L-type Ca2+ current (I(Ca,L)) remains controversial. We studied the effects of Ang II on I(Ca,L) in single adult rabbit ventricular myocytes using a perforated patch-clamp technique with gramicidin D. Ang II increased I(Ca,L) in a concentration-dependent manner (EC(50)=0.75 nM). In contrast, in conventional whole-cell patch-calmp, I(Ca,L)ran down gradually and the I(Ca,L) response to Ang II was variable, suggesting the potential loss of diffusible components crucial for the Ang II-induced signaling process. An AT(1) antagonist, CV11974 (0.1 microM), completely inhibited the increase in I(Ca,L) induced by Ang II (0.1 microM), whereas an AT(2) antagonist, PD123319 (10 microM), did not influence the I(Ca,L) increase. Neither pre- nor after-treatment with a Na+/H+ exchange (NHE) inhibitor HOE642 (1 microM) affected the Ang II-induced increase in I(Ca,L). The protein kinase C (PKC) inhibitor chelerythrine (1 microM) did not affect the Ang II-induced I(Ca,L) increase. The present findings indicate that Ang II increases I(Ca,L) via AT(1) receptors in adult rabbit ventricular myocytes. Neither the activation of NHE nor PKC may contribute to the Ang II-induced activation of I(Ca,L).
血管紧张素II（Ang II）对L型钙电流（I(Ca,L)）的影响仍存在争议。我们采用含短杆菌肽D的穿孔膜片钳技术，研究了Ang II对成年兔单个心室肌细胞I(Ca,L)的影响。Ang II以浓度依赖性方式增加I(Ca,L)（半数有效浓度[EC(50)] = 0.75 nM）。相比之下，在传统的全细胞膜片钳实验中，I(Ca,L)会逐渐衰减，并且I(Ca,L)对Ang II的反应不稳定，这表明对于Ang II诱导的信号传导过程至关重要的可扩散成分可能丢失。AT(1)拮抗剂CV11974（0.1 microM）可完全抑制Ang II（0.1 microM）诱导的I(Ca,L)增加，而AT(2)拮抗剂PD123319（10 microM）则不影响I(Ca,L)的增加。用Na+/H+交换（NHE）抑制剂HOE642（1 microM）预处理或后处理均不影响Ang II诱导的I(Ca,L)增加。蛋白激酶C（PKC）抑制剂白屈菜红碱（1 microM）不影响Ang II诱导的I(Ca,L)增加。目前的研究结果表明，在成年兔心室肌细胞中，Ang II通过AT(1)受体增加I(Ca,L)。NHE的激活和PKC均可能不参与Ang II诱导的I(Ca,L)激活。
