Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are membrane proteins encoded by four genes (HCN1-4) and widely distributed in the central and peripheral nervous system and in the heart. HCN channels are involved in several physiological functions, including the generation of rhythmic activity, and are considered important drug targets if compounds with isoform selectivity are developed. At present, however, few compounds are known, which are able to discriminate among HCN channel isoforms. The inclusion of the three-methylene chain of zatebradine into a cyclohexane ring gave a compound (3a) showing a 5-fold preference for HCN4 channels, and ability to selectively modulate Ih in different tissues. Compound 3a has been tested for its ability to reduce Ih and to interact with other ion channels in heart and CNS. Its preference for HCN4 channels makes this compound useful to elucidate the contribution of this isoform in the physiological and pathological processes involving hyperpolarization-activated current.

EC18 as a Tool To Understand the Role of HCN4 Channels in Mediating Hyperpolarization-Activated Current in Tissues / Maria Novella Romanelli, Martina Del Lungo, Luca Guandalini,Mehrnoush Zobeiri, Andras Gyokeres, TAmas Arpadffy-Lovas, Istvan Koncz, Laura Sartiani, Gian Luca Bartolucci, Silvia Dei, Dina Manetti, Elisabetta Teodori, Thomas Budde, Elisabetta Cerbai. - In: ACS MEDICINAL CHEMISTRY LETTERS. - ISSN 1948-5875. - ELETTRONICO. - 10:(2019), pp. 584-589. [10.1021/acsmedchemlett.8b00587]

EC18 as a Tool To Understand the Role of HCN4 Channels in Mediating Hyperpolarization-Activated Current in Tissues

Maria Novella Romanelli
;
Martina Del Lungo;Luca Guandalini;Laura Sartiani;Gian Luca Bartolucci;Silvia Dei;Dina Manetti;Elisabetta Teodori;Elisabetta Cerbai
2019

Abstract

Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are membrane proteins encoded by four genes (HCN1-4) and widely distributed in the central and peripheral nervous system and in the heart. HCN channels are involved in several physiological functions, including the generation of rhythmic activity, and are considered important drug targets if compounds with isoform selectivity are developed. At present, however, few compounds are known, which are able to discriminate among HCN channel isoforms. The inclusion of the three-methylene chain of zatebradine into a cyclohexane ring gave a compound (3a) showing a 5-fold preference for HCN4 channels, and ability to selectively modulate Ih in different tissues. Compound 3a has been tested for its ability to reduce Ih and to interact with other ion channels in heart and CNS. Its preference for HCN4 channels makes this compound useful to elucidate the contribution of this isoform in the physiological and pathological processes involving hyperpolarization-activated current.
2019
10
584
589
Maria Novella Romanelli, Martina Del Lungo, Luca Guandalini,Mehrnoush Zobeiri, Andras Gyokeres, TAmas Arpadffy-Lovas, Istvan Koncz, Laura Sartiani, Gian Luca Bartolucci, Silvia Dei, Dina Manetti, Elisabetta Teodori, Thomas Budde, Elisabetta Cerbai
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Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/1151825
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