Agonist | Tissue/Cell | Receptor Subtype (HCN Isoform) | Signaling Pathway | HCN-Mediated Effect | References |
---|---|---|---|---|---|
5-HT | SAN/atrium (human) | 5-HT4 | Gs/cAMP (↑) | Heart rate (↑) | Pino et al. (1998) and Lonardo et al. (2005) |
MSO (brainstem) | 5-HT1A | cAMP (↑) | Auditory system | Ko et al. (2016) | |
RTN (brainstem) | 5-HT7 | cAMP (↑) | Respiratory rhythm | Hawkins et al. (2015) | |
DRG | 5-HT7 | cAMP (↑) | Mechanical pain hypersensitivity (↓) | Santello and Nevian (2015) | |
Thalamocortical neurons | 5-HT1/2 (HCN2) | cAMP (↑) | Transmission of ascending inputs to cortex | McCormick and Pape (1990a, b) | |
ACh | SAN, atrium, AVN | M2 (HCN4, HCN2) | Gi/cAMP (↓) | Heart rate, conduction (↓) | DiFrancesco et al. (1989) |
ADO | SAN, atrium, AVN | A1 | Gi/cAMP (↓) | Heart rate, conduction (↓) | Zaza et al. (1996) and Porciatti et al. (1997) |
ANP | Atrium (human) | NP-A | cGMP→cAMP(↑) | Arrhythmias (?) | Lonardo et al. (2004) |
DA | PFC layer III pyramidal neurons | D1 (HCN?) | cAMP (↑) | Spatial working memory | Wang et al. (2007) and Arnsten and Jin (2014) |
NA | Heart | β1-AR | Gs/cAMP (↑) | Heart rate, conduction, arrhythmias (↑) | DiFrancesco and Tortora (1991) |
β2-AR | Gs-Gi/cAMP (↑) | Heart rate (↑) (arrhythmias?) | Cerbai et al. (1999a) and Barbuti et al. (2007) | ||
β3-AR | Gi/NO (?) | Not defined (↓Ih) | Sartiani et al. (2006) | ||
PMC layer V pyramidal neurons | α2-AR (HCN?) | Gi/cAMP (↓) | Voluntary movement | Sheets et al. (2011) | |
Thalamocortical neurons | α1-AR (HCN2) | cAMP (↑) | Transmission of ascending inputs to cortex | McCormick and Pape (1990a, b) | |
PFC layer III pyramidal neurons | α2-AR (HCN?) | cAMP (↓) | Spatial working memory | Wang et al. (2007) and Arnsten and Jin (2014) | |
PGE2 Substance P | DRG | ER | Gs/cAMP (↑) | Inflammatory pain | Jafri and Weinreich (1998), Momin et al. (2008), and Resta et al. (2016) |
Various (e.g., bradykinin, M1 agonist) | SAN | BK2, M1 (heterologously expressed HCN) | PLC/PI(4,5)P2 | (↑Ih) | Pian et al. (2007) |
ILN (thalamus) | Circadian rhythm | Zolles et al. (2006) and Ying et al. (2011) | |||
Pain | Pian et al. (2006, 2007) | ||||
— | Cell lines, DRG, SAN | (HCN1, HCN2, HCN4) | Src TK | HCN phosphorylation (↑Ih) or dephosphorylation (↓Ih) | Zong et al. (2005) |
RPTPs | Arinsburg et al. (2006) | ||||
Huang et al. (2008) |
ACh, acetylcholine; ADO, adenosine; A1, type-1 adenosine receptor; β1-, β2-, β3-AR, β-adrenergic receptor subtypes; BK2, type-2 bradykin receptor; D1, type-1 dopaminergic receptor; ER, prostglandin E2 receptor; ILN, intergeniculate nucleus; M1, type 1 muscarinic receptor; M2, type 2 muscarinic receptor; MSO, medial superior olive; NA, noradrenaline; NP-A, type-1 natriuretic peptide receptor; PFC, prefrontal cortex; PGE2, prostaglandin E2; PLC, phospholipase C; PMC, primary motor cortex; RPTP, receptor-like protein-tyrosine phosphatase; RTN, retrotrapezoid nucleus; Src TK, Src tyrosine kinase.