Itonaga Yasuhiro, Nakajima Tadasu, Morita Hiromitsu, Hanano Toyohisa, Miyauchi Yuji, Ito Yushi, Inoue Ryuji
Department of Pharmacology, Graduate School of Medical Sciences, Kyushu University, 812-8582, Fukuoka, Japan
Life Sci. 2002 Dec 20;72(4-5):487-500. doi: 10.1016/s0024-3205(02)02286-5.
We investigated a possible role of nifedipine-insensitive high voltage-activated (NI-HVA) Ca2+ channels in arterial diameter regulation in the semi-terminal branches of rabbit mesenteric artery (RMA). From these branches, NI-HVA Ca2+ currents showing almost identical properties to those previously identified in a similar region of guinea-pig [Circulation Research 1999;85:596-605] were recorded with whole-cell patch clamp recording. With video-microscopic measurement, the diameter of RMA segments perfused intraluminally at a constant rate (2-6 mL/h; 269 +/- 9 micro m, n = 27) decreased by 50-60% by raising the external K+ concentration ([K+]o) to 75 mM, a substantial part of which remained after addition of 1-10 micro M nifedipine (44 +/- 5% of initial diameter, n = 27). This nifedipine-insensitive diameter decrease (NI-DD) appeared to consist of initial transient and subsequent tonic phases (this separation was, however, not always clear), was resistant to tetrodotoxin, and was completely abolished in Ca2+-free or 100 micro M Cd2+-containing bath solutions. The magnitude of NI-DD increased depending on [K+]o with a threshold concentration of 20-40 mM. Raising the external Ca2+ concentration dose-dependently increased the magnitude of NI-DD, the extent being more prominent in the late tonic phase. Combined application of caffeine (10 mM) with ryanodine (3 micro M) produced a large transient NI-DD, which strongly attenuated the NI-DD evoked by a subsequent elevation in [K+]o. Using the fura-2 spectrofluorimetric Ca2+ imaging technique, a nifedipine-insensitive [Ca2+]i increase showing similar [K+]o-dependence and Cd2+ sensitivity to NI-DD was observed. These properties of NI-DD accord with those of NI-HVA Ca2+ channels, thus suggesting their contribution to small arterial diameter regulation in RMA.
我们研究了硝苯地平不敏感的高电压激活（NI-HVA）Ca2+通道在兔肠系膜动脉（RMA）半终末分支动脉直径调节中的可能作用。使用全细胞膜片钳记录技术，从这些分支中记录到的NI-HVA Ca2+电流，其特性与先前在豚鼠类似区域中鉴定的电流几乎相同[《循环研究》1999年；85:596 - 605]。通过视频显微镜测量，以恒定速率（2 - 6 mL/h；269 ± 9 μm，n = 27）腔内灌注的RMA节段直径，通过将细胞外K+浓度（[K+]o）提高到75 mM，直径降低了50 - 60%，在添加1 - 10 μM硝苯地平后，其中很大一部分仍然存在（初始直径的44 ± 5%，n = 27）。这种硝苯地平不敏感的直径减小（NI-DD）似乎由初始的瞬时相和随后的强直相组成（然而，这种分离并不总是清晰），对河豚毒素有抗性，并且在无Ca2+或含有100 μM Cd2+的浴液中完全消失。NI-DD的幅度随[K+]o增加而增加，阈值浓度为20 - 40 mM。提高细胞外Ca2+浓度剂量依赖性地增加NI-DD的幅度，在晚期强直相中这种增加更为显著。咖啡因（10 mM）与ryanodine（3 μM）联合应用产生了一个大的瞬时NI-DD，这强烈减弱了随后[K+]o升高所诱发的NI-DD。使用fura-2荧光光谱Ca2+成像技术，观察到一种硝苯地平不敏感的[Ca2+]i增加，其显示出与NI-DD相似的[K+]o依赖性和Cd2+敏感性。NI-DD的这些特性与NI-HVA Ca2+通道的特性一致，因此表明它们对RMA中小动脉直径调节有贡献。
