HCN4 channels
| Channel name | HCN41,2,3,4 |
| Description | Hyperpolarization-activated, cyclic nucleotide-gated cation channel |
| Other names | HAC4, BCNG3 |
| Molecular information | Human: 1203aa, NM_005477, NP_005468, chr. 15q24-q25 |
| Rat: 1198aa, NM_021658, NP_067690, chr. 8q24 | |
| Mouse: 1201aa, XM_287905, XP_287905, chr. 9 B | |
| Associated subunits | Not established |
| Functional assays | Voltage-clamp |
| Current | Ih, If, or Iq |
| Conductance | Not established |
| Ion selectivity | K+, Na+ (PNa/PK ∼ 0.2); divalents also permeate |
| Activation | V0.5 = -65 mV to -100 mV; ta = 260 ms-30s at -140 mV to -70 mV (values are strongly influenced by experimental parameters such as temperature, pH, and pulse protocol) |
| Inactivation | No inactivation |
| Activators | cAMP > cGMP (both include a positive shift of V0.5 in the range of +10 mV to +25 mV) |
| Gating modifiers | ZD7288 |
| Blockers | Cs+, ZD7288, ivabradine, zatebradine, cilobradine |
| Radioligands | None |
| Channel distribution | Thalamus, retina, olfactory bulb, sinus node, taste cells, testis |
| Physiological functions | Development of cardiac pacemaker cells, heart rate control, transduction of sour taste |
| Mutations and pathophysiology | D553N and HCN4-573X mutations associated with sick sinus node disease |
| Pharmacological significance | Not established |
aa, amino acids; chr., chromosome.
↵1. Ishii TM, Takano M, Xie LH, Noma A, and Ohmori H (1999) Molecular characterization of the hyperpolarization-activated cation channel in rabbit heart sinoatrial node. J Biol Chem 274:12835-12839
↵2. Ludwig A, Zong X, Stieber J, Hullin R, Hofmann F, and Biel M (1999) Two pacemaker channels from human heart with profoundly different activation kinetics. EMBO J 18:2323-2329
↵3. Monteggia LM, Eisch AJ, Tang MD, Kaczmarek LK, and Nestler EJ (2000) Cloning and localization of the hyperpolarization-activated cyclic nucleotide-gated channel family in rat brain. Brain Res Mol Brain Res 81:129-139
↵4. Seifert R, Scholten A, Gauss R, Mincheva A, Lichter P, and Kaupp UB (1999) Molecular characterization of a slowly gating human hyperpolarization-activated channel predominantly expressed in thalamus, heart, and testis. Proc Natl Acad Sci USA 96:9391-9396