HCN

2023-03-18:

HCN (Hyperpolarization-activated cyclic nucleotide–gated channel) #

• The pacemaker channel, making pacemaker currents.
• Opens by hyperpolarization and cAMP/cGMP/cCMP. It’s permeable to Na+ and K+, Thus it’s a $K_v$ Potassium Channel, and a CNG (cyclic nucleotide-gated) channel.
  • Wikipedia says they’re constitutively open at voltages near resting membrane potential?
  • Four subunits with 6 domains, which form: a voltage sensor, cyclic nueleotide-binding domain (CNBD) in the C-terminus, and a region carrying the “GYG triplet signature of K+-permeable channels,”
  • All 3 nucleotides are potent agonists but there’s some specificity among the subtypes.
• 4 Subtypes:
  • HCN1 channels have a more positive threshold for activation, faster activation kinetics, and a lower sensitivity to cAMP,
  • HCN2 and HCN3 have intermediate properties. cAMP is its primary agonist.
  • HCN4 channels are slowly gating and strongly sensitive to cAMP.
• When HCN is inhibited, serotonin fails to stimulate chemoreceptors in the RTN.