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Fig. 4 | Molecular Medicine

Fig. 4

From: Antiviral Drugs from the Nucleoside Analog Family Block Volume-Activated Chloride Channels

Fig. 4

AZT and acyclovir block the swelling-induced chloride current and regulatory volume decrease (RVD) in the human T cell lymphoma cell line H9

(a) In H9 cells (pulse protocol sec Fig. 1a), half maximal blockage can be observed at a concentration of ≈30 µM AZT added to the extracellular solution. Currents are leak subtracted. (b) Dose response curve for acyclovir added to the extracellular fluid (IC50 ≈ 20 µM). Currents are leak subtracted. (c) AZT significantly impedes regulatory volume decrease (RVD) in H9 cells: following reduction of extracellular osmolarity by 70 mosM H9 cells display instant cell swelling to 123.0 ± 1.1% (n = 8) in the absence (open symbols) and to 123.9 ± 0.6% (n = 9) in the presence of AZT (closed symbols). Under control conditions this cell swelling is followed by a gradual reduction of cell volume to 116.0 ± 0.9% (n = 6) within 240 sec after peak volume. In the presence of 100 µM AZT this volume decrease is diminished to 119.8 ± 0.7%. Thus RVD is significantly reduced from 30.3 ± 3% to 16.6 ± 3% in the presence of AZT (insert). The swelling experiments are given as actual volumes (V) divided by V0, where V0 is the mean of the first five measurements prior to the reduction of extracellular osmolarity versus time. RVD is expressed as loss of cell volume within 240 sec relative to the volume gained by the cells 60 sec after imposing the osmotic gradient. (d) The sensitivity of AZT for the cAMP-activated chloride current (IClcAMP) was measured in CaCo cells. In the presence of dbcAMP (0.5 mM), forskolin (0.01 mM), and IBMX (0.1 mM) a chloride current can be elicited ranging from +102.4 ± 60.3 pA (n = 5) to + 602.6 ± 189.9 pA (n = 5). Extracellular AZT in a concentration of 100 µM is without any significant effect on IClcAMP (+ 508.8 ± 191.1 pA; n = 5). NPPB in a concentration of 0.5 mM significantly reduces IClcAMP to + 120.0 ± 28.9 pA (n = 5).

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