Calcium-activated chloride conductance in a pancreatic adenocarcinoma cell line of ductal origin (HPAF) and in freshly isolated human pancreatic duct cells

Calcium-activated chloride conductance in a pancreatic adenocarcinoma cell line of ductal origin (HPAF) and in freshly isolated human pancreatic duct cells
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导管来源的胰腺腺癌细胞系 (HPAF) 和新鲜分离的人胰腺导管细胞中的钙激活氯离子电导

DOI:
10.1007/s004240050586
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发表时间:
1998
期刊:
Pflügers Archiv
影响因子:
--
通讯作者:
M. Gray
M. Gray
中科院分区:
--
文献类型:
--
作者:
J. Winpenny;A. Harris;M. Hollingsworth;B. Argent;M. Gray

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摘要 使用全细胞膜片钳技术,通过向浴液中添加 1 μM 离子霉素 (66 ± 22 pA/pF;Vm + 60 mV) 或向移液管溶液中添加 1 μM 钙 (136 ± 17 pA/pF;Vm + 60 mV),可以在 HPAF 细胞中引发钙激活氯电导 (CACC)。 Vm + 60 mV)。两种电导具有相似的生物物理特征,包括超极化电位下的时间依赖性失活以及线性/稍微向外的整流电流/电压(I/V)曲线,其反转电位(Erev)接近计算的氯离子平衡电位。由 Erev 位移获得的阴离子通透性序列为 I > Br ≥ Cl。 4,4'-二异硫氰酸芪二磺酸(DIDS,500 μM)对电流(Vm + 60 mV)产生 13% 的抑制,而 100 μM 格列本脲、30 nM TS-TM-calix[4]芳烃和 10 μM 他莫昔芬(所有氯离子通道阻滞剂)均无明显效果(8%、–6% 和–2% 抑制)。尼氟酸 (100 μM) 对电流产生电压依赖性抑制,分别为 48% 和 17%(Vm ± 60 mV)。在新鲜分离的人胰管细胞 (PDC) 中,用移液管溶液中的 1 μM 钙引发 CACC (260 ± 62 pA/pF;Vm + 60 mV)。人 PDC 中这种 CACC 的存在可以为治疗囊性纤维化中的人胰腺功能不全提供可能的治疗途径。
Abstract Using the whole-cell patch-clamp technique, a calcium-activated chloride conductance (CACC) could be elicited in HPAF cells by addition of 1 μM ionomycin to the bath solution (66 ± 22 pA/pF;Vm + 60 mV) or by addition of 1 μM calcium to the pipette solution (136 ± 17 pA/pF; Vm + 60 mV). Both conductances had similar biophysical characteristics, including time-dependent inactivation at hyperpolarising potentials and a linear/slightly outwardly rectifying current/voltage (I/V) curve with a reversal potential (Erev) close to the calculated cloride equilibrium potential. The anion permeability sequence obtained from shifts in Erev was I > Br ≥ Cl. 4,4′-Diisothiocyanatostilbene disulphonic acid (DIDS, 500 μM) caused a 13% inhibition of the current (Vm + 60 mV) while 100 μM glibenclamide, 30 nM TS-TM-calix[4]arene and 10 μM tamoxifen, all chloride channel blockers, had no marked effects (8%, –6% and –2% inhibition respectively). Niflumic acid (100 μM) caused a voltage-dependent inhibition of the current of 48% and 17% (Vm ± 60 mV, respectively). In freshly isolated human pancreatic duct cells (PDCs) a CACC was elicited with 1 μM calcium in the pipette solution (260 ± 62 pA/pF; Vm + 60 mV). The presence of this CACC in human PDCs could provide a possible therapeutic pathway for treatment of pancreatic insufficiency of the human pancreas in cystic fibrosis.
DOI: 10.1172/jci117709
发表时间: 1995
期刊: The Journal of clinical investigation.
影响因子: --
作者:
Husted,RF;Volk,KA;Sigmund,RD;Stokes,JB
通讯作者: Stokes,JB
DOI: 10.1073/pnas.87.13.4956
发表时间: 1990-07-01
影响因子: 11.1
作者:
CLIFF, WH;FRIZZELL, RA
通讯作者: FRIZZELL, RA