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