
IndraLab
Statements
3',5'-cyclic AMP binds HCN4. 9 / 9
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9
reach
"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."
reach
"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."
reach
"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)."