Characterization of the human HCN1 subunit and its inhibition by capsazepine

Gill, C.H., Bates, S.A., Owen, D., Larkman, P., Cairns, W., Yusuf, S., Murdock, P., Strijbos, P., Powell, A., Benham, C.D. and Davies, C.H. (2004) Characterization of the human HCN1 subunit and its inhibition by capsazepine. British Journal of Pharmacology (3). pp. 411-421. ISSN 0007-1188
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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.

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