硝苯地平及其他钙拮抗剂对猪尿道平滑肌细胞中格列本脲敏感钾电流的影响。

The effects of nifedipine and other calcium antagonists on the glibenclamide-sensitive K+ currents in smooth muscle cells from pig urethra.

作者信息

Teramoto N, Brading A F

机构信息

University Department of Pharmacology, Oxford.

出版信息

Br J Pharmacol. 1998 Apr;123(8):1601-8. doi: 10.1038/sj.bjp.0701777.

DOI:10.1038/sj.bjp.0701777

PMID:9605567

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1565332/

Abstract

The effects of nifedipine on both levcromakalim-induced membrane currents and unitary currents in pig proximal urethra were investigated by use of patch-clamp techniques (conventional whole-cell configuration and cell-attached patches). 2. Nifedipine had a voltage-dependent inhibitory effect on voltage-dependent Ba2+ currents at - 50 mV (Ki=30.6 nM). 3. In current-clamp mode, subsequent application of higher concentrations of nifedipine (> or =30 microM) caused a significant depolarization even after the membrane potential had been hyperpolarized to approximately -82 mV by application of 100 microM levcromakalim. 4. The 100 microM levcromakalim-induced inward current (symmetrical 140 mM K+ conditions, -50 mV) was inhibited by additional application of three different types of Ca antagonists (nifedipine, verapamil and diltiazem, all at 100 microM). In contrast, Bay K 8644 (1 microM) possessed no activating effect on the amplitude of this glibenclamide-sensitive current. 5. When 100 microM nifedipine was included in the pipette solution during conventional whole-cell recording at -50 mV, application of levcromakalim (100 microM) caused a significant inward membrane current which was suppressed by 5 microM glibenclamide. On the other hand, inclusion of 5 microM glibenclamide in the pipette solution prevented levcromakalim from inducing an inward membrane current. 6. The levcromakalim-induced K+ channel openings in cell-attached configuration were suppressed by subsequent application of 5 microM glibenclamide but not of 100 microM nifedipine. 7. These results suggest that in pig proximal urethra, nifedipine inhibits the glibenclamide-sensitive 43 pS K+ channel activity mainly through extracellular blocking actions on the K+ channel itself.

摘要

采用膜片钳技术（传统全细胞模式和细胞贴附式膜片）研究了硝苯地平对猪近端尿道中左卡尼汀诱导的膜电流和单位电流的影响。2. 硝苯地平对 -50 mV 时的电压依赖性 Ba2+ 电流具有电压依赖性抑制作用（Ki = 30.6 nM）。3. 在电流钳模式下，即使在通过应用 100 μM 左卡尼汀使膜电位超极化至约 -82 mV 后，随后应用更高浓度的硝苯地平（≥30 μM）仍会导致显著的去极化。4. 100 μM 左卡尼汀诱导的内向电流（对称 140 mM K+ 条件，-50 mV）在额外应用三种不同类型的钙拮抗剂（硝苯地平、维拉帕米和地尔硫䓬，均为 100 μM）后受到抑制。相比之下，Bay K 8644（1 μM）对这种格列本脲敏感电流的幅度没有激活作用。5. 在 -50 mV 进行传统全细胞记录时，当移液器溶液中含有 100 μM 硝苯地平时，应用左卡尼汀（100 μM）会引起显著的内向膜电流，该电流被 5 μM 格列本脲抑制。另一方面，移液器溶液中含有 5 μM 格列本脲可阻止左卡尼汀诱导内向膜电流。6. 在细胞贴附式模式下，左卡尼汀诱导的 K+ 通道开放在随后应用 5 μM 格列本脲时受到抑制，但 100 μM 硝苯地平则无此作用。7. 这些结果表明，在猪近端尿道中，硝苯地平主要通过对 K+ 通道本身的细胞外阻断作用来抑制格列本脲敏感的 43 pS K+ 通道活性。