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. 2012 Nov-Dec;6(6):438-42.
doi: 10.4161/chan.22209. Epub 2012 Sep 18.

Is ZD7288 a selective blocker of hyperpolarization-activated cyclic nucleotide-gated channel currents?

Xing Wu  1 , Liping Liao, Xiangming Liu, Fang Luo, Tianming Yang, Chenhong Li
Affiliations

Is ZD7288 a selective blocker of hyperpolarization-activated cyclic nucleotide-gated channel currents?

Xing Wu et al. Channels (Austin). 2012 Nov-Dec.

Abstract

ZD7288 has been widely used as a tool in the study of hyperpolarization-activated cyclic nucleotide-gated channels (HCN channels), and to test the relationships between HCN channels and heart and brain function. ZD7288 is widely considered a selective blocker of HCN currents. Here we show that ZD7288 inhibits not only HCN channel currents, but also Na(+) currents in DRG neurons and ZD7288 was confirmed to inhibit Na(+) current in HEK293 cells transfected with Na(v)1.4 plasmids. Thus our findings challenge the view that ZD7288 is a selective blocker of HCN channels. Conclusions about the role of NCN channels in neuronal function should be re-evaluated if based exclusively on the effect of ZD7288.

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Figures

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Figure 1. Na+ currents recorded in DRG neurons were identified by lidocaine, a selective blocker of sodium currents. (A) showed the Na+ currents recorded in a DRG neuron. Lidocaine almost completely inhibited the current, and the current could be recovered partially by washout. (B) Time course of current traces in the presence of Lidocaine (2 mM) recorded in response to 80 ms depolarizing pulses from -100 to -10 mV.
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Figure 2. Inhibition of Na+ currents in DRG neurons by ZD7288. (A1-A4) Traces were recorded in the presence and absence of different concentrations of ZD7288 and after washout of ZD7288. Time course of peak current amplitudes in the presence of different concentrations [100, 30, 10 and 1 (μM)] of ZD7288 recorded in response to 80 ms depolarizing pulses from -100 to -10 mV.
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Figure 3. Concentration-effect curve for ZD 7288 inhibition of Na+ currents. Normalized current is plotted against the logarithm of ZD 7288 concentration (μM) [100 (n = 3), 30 (n = 3), 10 (n = 4), 1 (n = 3), 0.1(n = 4) and 0.05 (n = 4)]. The data were fitted with the Hill equation.
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Figure 4. Inhibition of HCN current in DRG cells by ZD7288. (A) Traces were recorded in the absence and presence of ZD7288, at a range of concentrations r [0.1, 1, 5, 10, 30, 50, 100 (μM)]. DRG cells were whole-cell voltage clamped at -60 mV 100 ms and stepped to -140 mv for 700 ms and back to -70 mv for 300 ms to evoke HCN current. (B) Concentration-effect curve for ZD 7288 inhibition of HCN currents. Normalized current is plotted against the logarithm of ZD 7288 concentration (μM) [100 (n = 3), 30 (n = 4), 10 (n = 4), 1 (n = 3), 0.1(n = 3)]. The data were fitted with the Hill equation.
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Figure 5. Inhibition of recombinant Nav1.4 channels by ZD7288. (A) pcDNA3.1-Nav1.4 plasmids were transfected into HEK293 cells with GFP plasmids, and Nav1.4 channel currents were recorded in the absence, presence and after washout of ZD7288 (30μM). (B) Time course of peak current amplitude in the presence of ZD7288 (30μM) recorded in response to 80 ms depolarizing pulses from -100 to -10 mV.
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References

    1. Brown HF, DiFrancesco D, Noble SJ. How does adrenaline accelerate the heart? Nature. 1979;280:235–6. doi: 10.1038/280235a0. - DOI - PubMed
    1. Marshall PW, Rouse W, Briggs I, Hargreaves RB, Mills SD, McLoughlin BJ. ICI D7288, a novel sinoatrial node modulator. J Cardiovasc Pharmacol. 1993;21:902–6. doi: 10.1097/00005344-199306000-00008. - DOI - PubMed
    1. Luo L, Chang L, Brown SM, Ao H, Lee DH, Higuera ES, et al. Role of peripheral hyperpolarization-activated cyclic nucleotide-modulated channel pacemaker channels in acute and chronic pain models in the rat. Neuroscience. 2007;144:1477–85. doi: 10.1016/j.neuroscience.2006.10.048. - DOI - PubMed
    1. Li J, McRoberts JA, Nie J, Ennes HS, Mayer EA. Electrophysiological characterization of N-methyl-D-aspartate receptors in rat dorsal root ganglia neurons. Pain. 2004;109:443–52. doi: 10.1016/j.pain.2004.02.021. - DOI - PubMed
    1. Fan N, Sikand P, Donnelly DF, Ma C, Lamotte RH. Increased Na+ and K+ currents in small mouse dorsal root ganglion neurons after ganglion compression. J Neurophysiol. 2011;106:211–8. doi: 10.1152/jn.00065.2011. - DOI - PMC - PubMed

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