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

Research output: Contribution to journalArticlepeer-review

47 Citations (Scopus)

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 languageEnglish
Pages (from-to)411-421
JournalBritish Journal of Pharmacology
Volume143
Issue number3
DOIs
Publication statusPublished - 2004

Fingerprint

Dive into the research topics of 'Characterization of the human HCN1 subunit and its inhibition by capsazepine'. Together they form a unique fingerprint.

Cite this