Characterization of the human HCN1 subunit and its inhibition by capsazepine

C.H. Gill; S.A. Bates; D. Owen; P. Larkman; W. Cairns; S. Yusuf; P. Murdock; P. Strijbos; A. Powell; C.D. Benham; C.H. Davies

doi:10.1038/sj.bjp.0705945

Characterization of the human HCN1 subunit and its inhibition by capsazepine

C.H. Gill, S.A. Bates, D. Owen, P. Larkman, W. Cairns, S. Yusuf, P. Murdock, P. Strijbos, A. Powell, C.D. Benham, C.H. Davies

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Abstract

The human hyperpolarization-activated cyclic nucleotide-gated 1 (hHCN1) subunit was heterologously expressed in mammalian cell lines (CV-1 and CHO) and its properties investigated using whole-cell patch-clamp recordings. Activation of this recombinant channel, by membrane hyperpolarization, generated a slowly activating, noninactivating inward current.
The pharmacological properties of hHCN1-mediated currents resembled those of native hyperpolarization-activated currents (Ih), that is, blockade by Cs+ (99% at 5 mM), ZD 7288 (98% at 100 μM) and zatebradine (92% at 10 μM). Inhibition of the hHCN1-mediated current by ZD 7288 was apparently independent of prior channel activation (i.e. non-use-dependent), whereas that induced by zatebradine was use-dependent.

Original language	English
Pages (from-to)	411-421
Journal	British Journal of Pharmacology
Volume	143
Issue number	3
DOIs	https://doi.org/10.1038/sj.bjp.0705945
Publication status	Published - 2004

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title = "Characterization of the human HCN1 subunit and its inhibition by capsazepine",

abstract = "The human hyperpolarization-activated cyclic nucleotide-gated 1 (hHCN1) subunit was heterologously expressed in mammalian cell lines (CV-1 and CHO) and its properties investigated using whole-cell patch-clamp recordings. Activation of this recombinant channel, by membrane hyperpolarization, generated a slowly activating, noninactivating inward current. The pharmacological properties of hHCN1-mediated currents resembled those of native hyperpolarization-activated currents (Ih), that is, blockade by Cs+ (99% at 5 mM), ZD 7288 (98% at 100 μM) and zatebradine (92% at 10 μM). Inhibition of the hHCN1-mediated current by ZD 7288 was apparently independent of prior channel activation (i.e. non-use-dependent), whereas that induced by zatebradine was use-dependent.",

author = "C.H. Gill and S.A. Bates and D. Owen and P. Larkman and W. Cairns and S. Yusuf and P. Murdock and P. Strijbos and A. Powell and C.D. Benham and C.H. Davies",

note = "Original article can be found at: http://www.nature.com/bjp/index.html Copyright British Pharmacological Society and Nature Publishing Group. DOI: 10.1038/sj.bjp.0705945 [Full text of this article is not available in the UHRA]",

year = "2004",

doi = "10.1038/sj.bjp.0705945",

language = "English",

volume = "143",

pages = "411--421",

journal = "British Journal of Pharmacology",

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publisher = "Wiley-Blackwell",

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TY - JOUR

T1 - Characterization of the human HCN1 subunit and its inhibition by capsazepine

AU - Gill, C.H.

AU - Bates, S.A.

AU - Owen, D.

AU - Larkman, P.

AU - Cairns, W.

AU - Yusuf, S.

AU - Murdock, P.

AU - Strijbos, P.

AU - Powell, A.

AU - Benham, C.D.

AU - Davies, C.H.

N1 - Original article can be found at: http://www.nature.com/bjp/index.html Copyright British Pharmacological Society and Nature Publishing Group. DOI: 10.1038/sj.bjp.0705945 [Full text of this article is not available in the UHRA]

PY - 2004

Y1 - 2004

N2 - The human hyperpolarization-activated cyclic nucleotide-gated 1 (hHCN1) subunit was heterologously expressed in mammalian cell lines (CV-1 and CHO) and its properties investigated using whole-cell patch-clamp recordings. Activation of this recombinant channel, by membrane hyperpolarization, generated a slowly activating, noninactivating inward current. The pharmacological properties of hHCN1-mediated currents resembled those of native hyperpolarization-activated currents (Ih), that is, blockade by Cs+ (99% at 5 mM), ZD 7288 (98% at 100 μM) and zatebradine (92% at 10 μM). Inhibition of the hHCN1-mediated current by ZD 7288 was apparently independent of prior channel activation (i.e. non-use-dependent), whereas that induced by zatebradine was use-dependent.

AB - The human hyperpolarization-activated cyclic nucleotide-gated 1 (hHCN1) subunit was heterologously expressed in mammalian cell lines (CV-1 and CHO) and its properties investigated using whole-cell patch-clamp recordings. Activation of this recombinant channel, by membrane hyperpolarization, generated a slowly activating, noninactivating inward current. The pharmacological properties of hHCN1-mediated currents resembled those of native hyperpolarization-activated currents (Ih), that is, blockade by Cs+ (99% at 5 mM), ZD 7288 (98% at 100 μM) and zatebradine (92% at 10 μM). Inhibition of the hHCN1-mediated current by ZD 7288 was apparently independent of prior channel activation (i.e. non-use-dependent), whereas that induced by zatebradine was use-dependent.

U2 - 10.1038/sj.bjp.0705945

DO - 10.1038/sj.bjp.0705945

M3 - Article

SN - 0007-1188

VL - 143

SP - 411

EP - 421

JO - British Journal of Pharmacology

JF - British Journal of Pharmacology

IS - 3

ER -

Characterization of the human HCN1 subunit and its inhibition by capsazepine

Abstract

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