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

Wu, Xianning; Liao, Liping; Liu, Xiangming; Luo, Fang; Yang, Taowei; Li, Chenhong

doi:10.4161/chan.22209

Cited by 77 publications

(72 citation statements)

References 11 publications

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“…It is unlikely, however, that the effect of ZD7288 on T-type Ca 2+ channels contributes to the analgesic effects of ZD7288 that we have described in present study because ZD7288 is approximately 20 times more potent for HCN channels than for T-type Ca 2+ channels (Harris and Constanti, 1995;Seutin et al, 2001;Sa´nchez-Alonso et al, 2008). ZD7288 has been recently reported to be more effective in blocking Na + than HCN channel currents in DRG neurons in vitro (Wu et al, 2012), a finding that challenges the view that the analgesic effects of ZD7288 are mediated by HCN channels. Whether ZD7288 blocks Na + channels in vivo at low concentration reported by these investigators remains to be determined.…”

Section: Peripheral Blockade Of Hcn Channels Attenuates Spontaneous Pcontrasting

confidence: 46%

Increased expression of HCN2 channel protein in L4 dorsal root ganglion neurons following axotomy of L5- and inflammation of L4-spinal nerves in rats

Smith¹,

Otaibi²,

Sathish³

et al. 2015

Neuroscience

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Section: Peripheral Blockade Of Hcn Channels Attenuates Spontaneous Pcontrasting

confidence: 46%

Increased expression of HCN2 channel protein in L4 dorsal root ganglion neurons following axotomy of L5- and inflammation of L4-spinal nerves in rats

Smith¹,

Otaibi²,

Sathish³

et al. 2015

Neuroscience

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“…Ion channels other than the low-voltage-activated K + channels and the HCN channels may also participate in controlling the firing patterns of VGCs, since influence of a given current on a neuron's activity is dependent on all of the ion channels present in the membrane (Marder and Goaillard, 2006). It is possible that some unspecific effects of ZD7288 on other ion channels than the HCN channels had some effects on the shape of APs in VGCs (Sanchez-Alonso et al, 2008;Wu et al, 2012). The distribution of firing patterns of rat VGCs underwent considerable developmental changes.…”

Section: Discussionmentioning

confidence: 98%

Developmental increase in hyperpolarization-activated current regulates intrinsic firing properties in rat vestibular ganglion cells

et al. 2015

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“…The hyperpolarisation-activated current (I h ) is a mixed cationic current carried by Na + and K + and recent evidence for small but significant Ca 2+ permeability of these channels [32]. The role of HCN channels has been well documented in pace-making cells in the sinoatrial node and in the brain [33]. I h is activated by hyperpolarisation to potentials negative to -50 to -60mV and inactivates upon depolarisation.…”

Section: Discussionmentioning

confidence: 99%

“…Further support for the existence of HCN channels in modulating rhythmic contractions is provided by our MEA data where ZD7288 significantly reduced peak-to-peak LFP amplitude. While the precise localisation of these channels requires further investigation, it is known that among striated muscle fibres there are contracting-filament-fibres which resemble the bundle of His of blood heart in the lymph heart [33] making it likely that these channels are located in that area.…”

Section: Discussionmentioning

confidence: 99%

Characterisation of Development and Electrophysiological Mechanisms Underlying Rhythmicity of the Avian Lymph Heart

et al. 2016

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Despite significant advances in tissue engineering such as the use of scaffolds, bioreactors and pluripotent stem cells, effective cardiac tissue engineering for therapeutic purposes has remained a largely intractable challenge. For this area to capitalise on such advances, a novel approach may be to unravel the physiological mechanisms underlying the development of tissues that exhibit rhythmic contraction yet do not originate from the cardiac lineage. Considerable attention has been focused on the physiology of the avian lymph heart, a discrete organ with skeletal muscle origins yet which displays pacemaker properties normally only found in the heart. A functional lymph heart is essential for avian survival and growth in ovo. The histological nature of the lymph heart is similar to skeletal muscle although molecular and bioelectrical characterisation during development to assess mechanisms that contribute towards lymph heart contractile rhythmicity have not been undertaken. A better understanding of these processes may provide exploitable insights for therapeutic rhythmically contractile tissue engineering approaches in this area of significant unmet clinical need. Here, using molecular and electrophysiological approaches, we describe the molecular development of the lymph heart to understand how this skeletal muscle becomes fully functional during discrete in ovo stages of development. Our results show that the lymph heart does not follow the normal transitional programme of myogenesis as documented in most skeletal muscle, but instead develops through a concurrent programme of precursor expansion, commitment to myogenesis and functional differentiation which offers a mechanistic explanation for its rapid development. Extracellular electrophysiological field potential recordings revealed that the peak-to-peak amplitude of electrically evoked local field potentials elicited from isolated lymph heart were significantly reduced by treatment with carbachol; an effect that could be fully reversed by atropine. Moreover, nifedipine and cyclopiazonic acid both significantly reduced peak-to-peak local field potential amplitude. Optical recordings of lymph heart showed that the organ’s rhythmicity can be blocked by the HCN channel blocker, ZD7288; an effect also associated with a significant reduction in peak-to-peak local field potential amplitude. Additionally, we also show that isoforms of HCN channels are expressed in avian lymph heart. These results demonstrate that cholinergic signalling and L-type Ca2+ channels are important in excitation and contraction coupling, while HCN channels contribute to maintenance of lymph heart rhythmicity.

show abstract

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

Cited by 77 publications

References 11 publications

Increased expression of HCN2 channel protein in L4 dorsal root ganglion neurons following axotomy of L5- and inflammation of L4-spinal nerves in rats

Increased expression of HCN2 channel protein in L4 dorsal root ganglion neurons following axotomy of L5- and inflammation of L4-spinal nerves in rats

Developmental increase in hyperpolarization-activated current regulates intrinsic firing properties in rat vestibular ganglion cells

Characterisation of Development and Electrophysiological Mechanisms Underlying Rhythmicity of the Avian Lymph Heart

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