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Cardiac Channels: Hyperpolarization-activated Cyclic Nucleotide-Gated Channels (HCN1-4) Antibodies
Biological rhythms (beating of the heart,
circadian sleep cycles, respiration, and the release of hormones) are necessary
to sustain life. Heart beating is the most reliable and rhythmic biological
phenomenon. Cardiac pacemaking is produced by the slow diastolic depolarization
phase of the action potential. The hyperpolarization-activated cation current
(termed If, Ih, or Iq) plays a key role in the in the initiation and modulation
of cardiac and neuronal pacemaker depolarization. The generation of cardiac
pacemaker potentials relies on a complex interplay between at least four
different types of cation channels: T- and L-type Ca2+ channels, K+ channels,
and a cation channel termed If (synonymous names are Ih and Iq). The If channel
has been designated as "pacemaker" channel because it reveals unique features
that are believed to be a prerequisite for pacemaker activity. Recently, the
hyperpolarization-activated cyclic nucleotide-gated
families of ion channel proteins (HCN1-4) have been identified as the
"pacemaker" channel. The amino acid sequences of HCNs predict a structure
similar to that of voltage-gated (Kv) channels and cyclic nucleotide-gated (CNG)
channels. HCNs proteins (HCN1-4) are characterized by six transmembrane domains
(S1-S6), including a including a positively charged voltage-sensing S4 segment
and an ion-conducting pore between S5 and S6. In the C terminus the HCNs carry a
cyclic nucleotide-binding domain (CNBD), a motif found in several cyclic
nucleotide-binding proteins. The core region of HCNs channels (S1 to the C
terminus of the CNBD) is highly conserved, whereas the cytoplasmic N and
C-termini, HCN1, also known as Brain cyclic nucleotide channel gated 1, BCNG1 or HAC-2 (mouse/rat 910 aa, human 749-aa), is primarily expressed in brain. In mouse, HCN1 is mainly expressed in the neocortex, the CA1 region of the hippocampus, the superior colliculus, and in the molecular cell layer of the cerebellum. HCN2, also known as Brain cyclic nucleotide channel gated 2, BCNG2 or HAC-1 (rat 834 aa, human 889-aa, chromosome 19p13.3), is primarily expressed in brain. In mouse, HCN1 is mainly expressed in brain (olfactory bulb and cerebral cortex, hippocampus, thalamus, cerebellum etc) and heart (ventricles and atrium). HCN3 or HAC3 (rat 780-aa, mouse 779-aa, human 703 aa) has been detected in brain but its expression was much less than other HCNs. Its expression was also detected in liver, lung, and kidney of mouse by some researchers but not by others. HCN4 (rat 1198 aa,
human 1203-aa, chromosome 15q24-q25) is highly expressed at heart ventricle and
atrium, brain (olfactory bulb, thalamus), and testis. expressed in brain.
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© 2005 GENTAUR bvba |