Hyperpolarization-activated, cyclic channels

Zong, X., Eckert, C., Yuan, H., Wahl-Schott, C., Abicht, H., Fang, L., et al. (2005) A novel mechanism of modulation of hyperpolarization-activated cyclic nucleotidegated channels by Src kinase. J Biol Chem 280, 34224-34232. 

Barco A, Alarcon JM, Kandel ER (2002) Expression of constitutively active CREB protein facilitates the late phase of long-term potentiation by enhancing synaptic capture. Cell 108 689-703 Bear MF, Malenka RC (1994) Synaptic plasticity LTP and LTD. Curr Opin Neurobiol 4 389-99 Bender RA, Brewster A, Santoro B, Ludwig A, Hofmann F, Biel M, Baram TZ (2001) Differential and age-dependent expression of hyperpolarization-activated, cyclic nucleotide-gated cation channel isoforms 1 1 suggests evolving roles in the developing rat hippocampus. Neuroscience 106 689-98... 

Sour taste detects acids, i.e., protons. Several different sour taste receptor candidates such as acid-sensing ion channels (ASICs) (57), hyperpolarization-activated cyclic nucleotide-gated channels (HCNs) (58), and two pore domain potassium channels (K2PS) (59, 60) have been described in the past. In addition, recent research identified two members of the polycystic kidney disease (PKD) family of the transient receptor potential superfamily (TRP) as strong sour taste receptor candidates or as part thereof. Immunohistochemistry and in situ hybridization revealed the presence of the polycystic-kidney-disease-like ion channel PKD2L1 in subsets of taste receptor cells of mouse fungiform, vallate, and foliate papillae. These cells differ from... 

In the myocardium, automaticity is the ability of the cardiac muscle to depolarize spontaneously (i.e., without external electrical stimulation from the autonomic nervous system). This spontaneous depolarization is due to the plasma membrane within the heart that has reduced permeability to potassium (K+) but still allows passive transfer of calcium ions, allowing a net charge to build. Automaticity is most often demonstrated in the sinoatrial (SA) node, the so-called pacemaker cells. Abnormalities in automaticity result in rhythm changes. The mechanism of automaticity involves the pacemaker channels of the HCN (Hyperpolarization-activated, Cyclic Nucleotide-gated) family14 (e.g., If, "funny" current). These poorly selective cation channels conduct more current as the membrane potential becomes more negative, or hyperpolarized. They conduct both potassium and sodium ions. The activity of these channels in the SA node cells causes the membrane potential to slowly become more positive (depolarized) until, eventually, calcium channels are activated and an action potential is initiated. 

Pachucki, J., Burmeister, L.A. and Larsen, P.R. (1999) Thyroid hormone regulates hyperpolarization-activated cyclic nucleotide-gated channel (HCN2) mRNA in the rat heart. Circulation Research, 85, 498-503. 

Cyclic nucleotide-modulated channels consist of two groups the cyclic nucleotide—gated (CNG) channels, which play key roles in sensory transduction for olfactory and photoreceptors, and the hyperpolarization-activated, cyclic nucleotide-gated (HCN) channels. HCN channels are cation channels that open with hyperpolarization and close with depolarization upon direct binding of cyclic AMP or cyclic GMP, the activation curves for the channels are shifted to more hyper-polarized potentials. These channels play essential roles in cardiac pacemaker cells and presumably in rhythmically discharging neurons. 

Hyperpolarization-Activated Cyclic-Nucleotide-Gated Channels... 

Yeon K-Y, Chung G, Kim YH, Hwang JH, Davies AJ, Park M-K, Ahn DK, Kim JS, Jung SJ, Oh SB (2011) Eugenol reverses mechanical allodynia after peripheral nerve injury by inhibiting hyperpolarization-activated cyclic nucleotide-gated (HCN) channels. Pain 152 2108-2116... 

Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels Potapova Potapova et al., 2004... 

Vasylyev, D. Lu, Q. Mark, B. Edward, K. Shan, Q. High-throughput screening of modulators of hyperpolarization-activated cyclic nucleotide-gated (HCN) channels. PCT Int. Appl. WO 2008121735, 2008 Chem. Abstr. 2008, 149, 455063. 

Hyperpolarization-activated and Cyclic Nucleotide-gated Channels (HCN)... 

Cyclic nucleotide-modulated ion channels (Table 6-2) are not K+-selective. Nevertheless, their inward current of Na+ and Ca2+ ions is conducted through a channel that is similar in overall architecture to Shaker K+ channels. This protein family includes the CNG channels, which respond only to cyclic nucleotides, and the HCN channels, which are activated synergistically by hyperpolarization and cyclic nucleotide binding [38,40]. The CNG channels are involved in signaling of visual and olfactory information and serve as cyclic nucleotide-gated Ca2+ channels. In contrast, the HCN channels are required for normal rhythmic electrical discharges by the sinoatrial node in the heart and the pacemaker cells of the thalamus. 

Membrane depolarization typically results from an increase in Na+ conductance. In addition, mobilization of intracellular Ca2+ from the endoplasmic or sarcoplasmic reticulum and the influx of extracellular Ca2+ appear to be elicited by ACh acting on muscarinic receptors (see Ch. 22). The resulting increase in intracellular free Ca2+ is involved in activation of contractile, metabolic and secretory events. Stimulation of muscarinic receptors has been linked to changes in cyclic nucleotide concentrations. Reductions in cAMP concentrations and increases in cGMP concentrations are typical responses (see Ch. 21). These cyclic nucleotides may facilitate contraction or relaxation, depending on the particular tissue. Inhibitory responses also are associated with membrane hyperpolarization, and this is a consequence of an increased K+ conductance. Increases in K+ conductance may be mediated by a direct receptor linkage to a K+ channel or by increases in intracellular Ca2+, which in turn activate K+ channels. Mechanisms by which muscarinic receptors couple to multiple cellular responses are considered later. 

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