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3',5'-cyclic AMP binds HCN4. 19 / 19
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"Sympathetic stimulation increases cAMP in SAMs, and binding of cAMP to HCN4 channels shifts pore opening to more depolarized membrane potentials and slows channel closing."
31756134
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"The values of cAMP binding to the tetrameric HCN4 C-terminal region, which were determined by ITC, were utilized in the same way as for the HCN4 channel data ( Fig. 3 ; Table 1 )."
35219649
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"We found that cAMP and cGMP bind to both the wild-type and mutant tetrameric HCN4 C-terminal regions with negative cooperativity, as we found previously for cAMP binding to the wild-type HCN4 as well [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
35219649
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"While cAMP binding to HCN4 modulates I f activation (XREF_FIG), studies in which either HCN2 or HCN4 channel were genetically modified in mice, and prior studies in which I f current was blocked in numerous species by ionic or pharmacological maneuvers, do not indicate that I f is required for the SANC basal beating rate, or for its modulation by beta-AR stimulation."
20156611
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"However, cAMP-modulated I current in the mice VB is mainly driven by HCN2 channels [39] even though HCN4 can bind cAMP with high affinity, its expression in the VB is not sufficient enough to rescue the cAMP-modulated current in the I in the HCN2EA VB [23]."
37239964
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"Studies using transition ion metal FRET, double electron-electron resonance, and NMR have suggested that cAMP binding to the HCN2 and HCN4 C-terminal regions shifts the B- and C-helices of the CNBD toward the β-roll, and that the secondary structures of the P- and C-helices become more stable (Taraska et al., 2009; Puljung and Zagotta, 2013; Puljung et al., 2014; Saponaro et al., 2014; Akimoto et al., 2014; Akimoto et al., 2018)."
31481514
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"We studied the role of I (f) in mice, in which binding of cAMP to HCN4 channels was abolished by a single amino-acid exchange (R669Q)."
18219271
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"By introducing the knock-in mutation R669Q in the CNBD, binding of cAMP to HCN4 channels was abolished."
34129872
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"This depolarizing shift in voltage dependence appeared to result from direct binding of cAMP to HCN4 because it was eliminated by a point mutation (R669Q) at a conserved arginine in the CNBD that has been shown to disrupt cAMP binding to HCN4 and other cyclic nucleotide sensitive ion channels."
23109717
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"By exchange of arginine 669 to glutamine, binding of cAMP to HCN4 channels was abolished."
19351513
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"Moreover, by binding to HCN4, cAMP raises the embryonic heart rate to a level essential for survival."
19351513
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"42 Similar observations were made in adult heterozygous knock-in mice expressing a cAMP binding deficient HCN4 subunit."
21499520
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"For the protein sample used to solve the structure of HCN4 bound to cAMP, the ligand (Sigma-Aldrich) was kept at a concentration of 0.2 mM in all steps of membrane isolation and protein purification procedure described above."
34166608
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"In contrast to knockout of RyR2, NCX or CaMKII function, or Ankyrin-B, or mutations in human RyRs, genetic manipulation in mice including HCN2 or HCN4 (general or cardiac specific SA node and AV node) knock outs, or inhibition of cAMP binding to HCN4 subunits, have minimal or no effects on resting heart rate, or on increases in heart rate during exercise, or chronotropic effect of beta-AR stimulation (XREF_SUPPLEMENTARY)."
20203315
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"I (f) is produced by hyperpolarization activated cyclic nucleotide sensitive-4 (HCN4) channels, and it is widely believed that sympathetic regulation of I (f) occurs via direct binding of cAMP to HCN4, independent of phosphorylation."
21150293
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"Mice with a homozygous mutation of a single amino-acid exchange (R669Q) that prevented binding of cAMP to HCN4 channels, HCN4 R669Q and R669Q mice, are also embryonic lethal [XREF_BIBR]."
19573534
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"The study by Xu et al. first examined steady-state binding of cAMP to an isolated HCN4 C-linker-CNBD fragment (called CL-CNBD) by using two different equilibrium binding assays, isothermal titration calorimetry and fluorescence anisotropy."
23217679
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"To identify candidate amino acids making significant contributions to the HCN4 temperature response, we used a common-sense approach: focusing our search on residues of protein regions exhibiting significative changes in SASA measured between the two states represented by the structures of the cAMP-free (closed) and cAMP-bound (activated) states of the HCN4 channel.We performed a comparison of the human HCN4 structures with homology models of similar channels, including from Tardigrade (Ramazzottius varieornatus), an organism resistant to extreme heat."
37693513
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"A comparison of cAMP and cGMP binding to the wild-type HCN4 C-terminal tetramer shows differences."
35219649