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Hypoxia augments the calcium-activated chloride current carried by anoctamin-1 in cardiac vascular endothelial cells of neonatal mice.

Wu MM, Lou J, Song BL, Gong YF, Li YC, Yu CJ, Wang QS, Ma TX, Ma K, Hartzell HC, Duan DD, Zhao D, Zhang ZR - Br. J. Pharmacol. (2014)

Bottom Line: The density of ICl ( C a) detected in CVECs was significantly inhibited by T16Ainh -A01, an Ano1 inhibitor, and a pore-targeting, specific anti-Ano1 antibody, and was markedly decreased in Ano1 gene knockdown CVECs.Ano1 formed CaCC in CVECs of neonatal mice.Ano1 may play a role in the pathophysiological processes during ischaemia in heart, and therefore, Ano1 might be a potential therapeutic target to prevent ischaemic damage.

View Article: PubMed Central - PubMed

Affiliation: Departments of Clinical Pharmacy and Cardiology, Institute of Clinical Pharmacy, The 2nd Affiliated Hospital, Key Laboratories of Education Ministry for Myocardial Ischemia Mechanism and Treatment, Harbin Medical University, Harbin, China.

No MeSH data available.


Related in: MedlinePlus

Representative macroscopic current traces were respectively recorded from CVECs with the voltage protocol depicted in the inset, in the presence of NaCl (A and D), Na-gluconate (B) or NaNO3 (E). The steady-state current densities obtained from indicated experimental conditions were plotted as a function of membrane potentials (C and F) (n = 5–8 for different data points). (G–I) Representative macroscopic current traces were respectively recorded from a CVEC under control condition (G) or in the presence of 100 μM NFA (H), and followed by washing out NFA (I). (J) Steady-state I–V relationships show that the current was significantly blocked by 100 μM NFA (n = 6).
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fig02: Representative macroscopic current traces were respectively recorded from CVECs with the voltage protocol depicted in the inset, in the presence of NaCl (A and D), Na-gluconate (B) or NaNO3 (E). The steady-state current densities obtained from indicated experimental conditions were plotted as a function of membrane potentials (C and F) (n = 5–8 for different data points). (G–I) Representative macroscopic current traces were respectively recorded from a CVEC under control condition (G) or in the presence of 100 μM NFA (H), and followed by washing out NFA (I). (J) Steady-state I–V relationships show that the current was significantly blocked by 100 μM NFA (n = 6).

Mentions: For the rest of the experiments, 777 nM free [Ca2+]i was used. We assessed anion selectivity experiments to determine whether the voltage- and Ca2+-dependent macroscopic current is mediated by a chloride channel. The magnitude of outward currents was significantly reduced by replacing extracellular Cl− with gluconate−, and the Vrev shifted from near zero (−1.37 ± 0.79 mV) to depolarizing potential (52.5 ± 2.31 mV) (n = 5) (Fig. 2A–C). Substitution of extracellular Cl− with NO3− resulted in a dramatic increase in the amplitude of outward current, and the Vrev shifted from near zero (−0.92 ± 0.68 mV) to hyperpolarizing potentials (−23.11 ± 1.04 mV) (n = 8) (Fig. 2D–F). The relative permeability ratios for Pglu/PCl and PNO3/PCl were 0.13 ± 0.01 and 2.30 ± 0.10. Moreover, the macroscopic current was reversibly blocked by 100 μM niflumic acid (NFA), a non-specific chloride channel blocker (n = 6) (Fig. 2G–J). These data together suggest that the voltage- and Ca2+-dependent current recorded from CVECs is mediated by a chloride channel.


Hypoxia augments the calcium-activated chloride current carried by anoctamin-1 in cardiac vascular endothelial cells of neonatal mice.

Wu MM, Lou J, Song BL, Gong YF, Li YC, Yu CJ, Wang QS, Ma TX, Ma K, Hartzell HC, Duan DD, Zhao D, Zhang ZR - Br. J. Pharmacol. (2014)

Representative macroscopic current traces were respectively recorded from CVECs with the voltage protocol depicted in the inset, in the presence of NaCl (A and D), Na-gluconate (B) or NaNO3 (E). The steady-state current densities obtained from indicated experimental conditions were plotted as a function of membrane potentials (C and F) (n = 5–8 for different data points). (G–I) Representative macroscopic current traces were respectively recorded from a CVEC under control condition (G) or in the presence of 100 μM NFA (H), and followed by washing out NFA (I). (J) Steady-state I–V relationships show that the current was significantly blocked by 100 μM NFA (n = 6).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4128065&req=5

fig02: Representative macroscopic current traces were respectively recorded from CVECs with the voltage protocol depicted in the inset, in the presence of NaCl (A and D), Na-gluconate (B) or NaNO3 (E). The steady-state current densities obtained from indicated experimental conditions were plotted as a function of membrane potentials (C and F) (n = 5–8 for different data points). (G–I) Representative macroscopic current traces were respectively recorded from a CVEC under control condition (G) or in the presence of 100 μM NFA (H), and followed by washing out NFA (I). (J) Steady-state I–V relationships show that the current was significantly blocked by 100 μM NFA (n = 6).
Mentions: For the rest of the experiments, 777 nM free [Ca2+]i was used. We assessed anion selectivity experiments to determine whether the voltage- and Ca2+-dependent macroscopic current is mediated by a chloride channel. The magnitude of outward currents was significantly reduced by replacing extracellular Cl− with gluconate−, and the Vrev shifted from near zero (−1.37 ± 0.79 mV) to depolarizing potential (52.5 ± 2.31 mV) (n = 5) (Fig. 2A–C). Substitution of extracellular Cl− with NO3− resulted in a dramatic increase in the amplitude of outward current, and the Vrev shifted from near zero (−0.92 ± 0.68 mV) to hyperpolarizing potentials (−23.11 ± 1.04 mV) (n = 8) (Fig. 2D–F). The relative permeability ratios for Pglu/PCl and PNO3/PCl were 0.13 ± 0.01 and 2.30 ± 0.10. Moreover, the macroscopic current was reversibly blocked by 100 μM niflumic acid (NFA), a non-specific chloride channel blocker (n = 6) (Fig. 2G–J). These data together suggest that the voltage- and Ca2+-dependent current recorded from CVECs is mediated by a chloride channel.

Bottom Line: The density of ICl ( C a) detected in CVECs was significantly inhibited by T16Ainh -A01, an Ano1 inhibitor, and a pore-targeting, specific anti-Ano1 antibody, and was markedly decreased in Ano1 gene knockdown CVECs.Ano1 formed CaCC in CVECs of neonatal mice.Ano1 may play a role in the pathophysiological processes during ischaemia in heart, and therefore, Ano1 might be a potential therapeutic target to prevent ischaemic damage.

View Article: PubMed Central - PubMed

Affiliation: Departments of Clinical Pharmacy and Cardiology, Institute of Clinical Pharmacy, The 2nd Affiliated Hospital, Key Laboratories of Education Ministry for Myocardial Ischemia Mechanism and Treatment, Harbin Medical University, Harbin, China.

No MeSH data available.


Related in: MedlinePlus