Reduced functional expression of K+ channels in vascular smooth muscle cells from rats made hypertensive with Nω-nitro-L-arginine
Reduced functional expression of K+ channels in vascular smooth muscle cells from rats made hypertensive with Nω-nitro-L-arginine
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DOI：
10.1152/ajpheart.01053.2004
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发表时间：
2005-09-01
影响因子：
4.8
通讯作者：
Dick, GM
中科院分区：
文献类型：
--
作者：
Bratz, IN;Swafford, AN;Dick, GM
平滑肌膜电位部分由K+通道决定。在本文的配套论文中（Bratz In, Dick GM， Partridge LD和Kanagy NL）。[J] .中国心脏杂志，2005)，我们证明了用n -omega-硝基- l -精氨酸（L-NNA）治疗高血压大鼠的肠系膜上动脉与正常血压大鼠相比去极化和表达较少的K+通道蛋白。在本研究中，我们使用膜片钳技术来验证l - rna诱导的高血压降低平滑肌中K+通道的功能表达的假设。在全细胞实验中，使用无Ca2+移液管溶液，电流为0 mV，主要是由于电压依赖性K+ (K- v)通道，高血压降低了60% （2.7 +/- 0.4 vs. 1.1 +/- 0.2 pA/pF）。在+100 mV和300 nM游离Ca2+电流下，主要是由于大电导Ca2+激活的K+ (BKCa)通道，高血压降低了40% （181 +/- 24 vs. 101 +/- 28 pA/pF）。被3mm 4-氨基吡啶阻断的电流（一种多种K-V通道类型的抑制剂）在高血压中减少了50% （1.0 +/- 0.4 vs. 0.5 +/- 0.2 pA/pF）。1 mM四乙基铵（一种BKCa通道抑制剂）阻断的电流在高血压患者中减少了40% （86 +/- 14 vs 53 +/- 19 pA/pF）。BKCa电流大小的差异不归因于单通道电导或Ca2+/电压敏感性的变化。这些数据支持l - rna诱导的高血压降低血管平滑肌K+电流的假设。K+通道的分子和功能表达减少可能部分解释了l - rna处理大鼠平滑肌的去极化和收缩敏感性增强。
Smooth muscle membrane potential is determined, in part, by K+ channels. In the companion paper to this article (Bratz IN, Dick GM, Partridge LD, and Kanagy NL. Am J Physiol Heart Circ Physiol 289: H1277-H1283, 2005), we demonstrated that superior mesenteric arteries from rats made hypertensive with N-omega-nitro-L-arginine (L-NNA) are depolarized and express less K+ channel protein compared with those from normotensive rats. In the present study, we used patch-clamp techniques to test the hypothesis that L-NNA-induced hypertension reduces the functional expression of K+ channels in smooth muscle. In whole cell experiments using a Ca2+-free pipette solution, current at 0 mV, largely due to voltage-dependent K+ (K-V) channels, was reduced similar to 60% by hypertension (2.7 +/- 0.4 vs. 1.1 +/- 0.2 pA/pF). Current at +100 mV with 300 nM free Ca2+, largely due to large-conductance Ca2+-activated K+ (BKCa) channels, was reduced similar to 40% by hypertension (181 +/- 24 vs. 101 +/- 28 pA/pF). Current blocked by 3 mM 4-aminopyridine, an inhibitor of many K-V channel types, was reduced similar to 50% by hypertension (1.0 +/- 0.4 vs. 0.5 +/- 0.2 pA/pF). Current blocked by 1 mM tetraethylammonium, an inhibitor of BKCa channels, was reduced similar to 40% by hypertension (86 +/- 14 vs. 53 +/- 19 pA/pF). Differences in BKCa current magnitude are not attributable to changes in single-channel conductance or Ca2+/voltage sensitivity. The data support the hypothesis that L-NNA-induced hypertension reduces K+ current in vascular smooth muscle. Reduced molecular and functional expression of K+ channels may partly explain the depolarization and augmented contractile sensitivity of smooth muscle from L-NNA-treated rats.