Structural and functional determinants in the S5-P region of HCN-encoded pacemaker channels revealed by cysteine-scanning substitutions

American Journal of Physiology - Cell Physiology

Volumn 294, Issue 1, 2008, Pages

  Au, Ka Wing ^a   Siu, Chung Wah ^a,b,c   Lau, Chu Pak ^a   Tse, Hung Fat ^a   Li, Ronald A ^a,b,c,d  

^a UNIVERSITY OF HONG KONG   (Hong Kong)

^b UNIVERSITY OF CALIFORNIA   (United States)

^c UNIVERSITY OF CALIFORNIA   (United States)

^d SHRINERS HOSPITALS FOR CHILDREN NORTHERN CALIFORNIA   (United States)

Author keywords

Cysteine mutagenesis; Hyperpolarization activated cyclic nucleotide; Sulfhydryl modification

Indexed keywords

CADMIUM; CYSTEINE; METHANETHIOSULFATE ETHYLAMMONIUM; THIOL DERIVATIVE; UNCLASSIFIED DRUG;

AMINO ACID SUBSTITUTION; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BIOENERGY; CHANNEL GATING; CONTROLLED STUDY; FEMALE; HYPERPOLARIZATION; MEMBRANE CURRENT; MOUSE; MUTAGENESIS; NONHUMAN; PHENOTYPE; PRIORITY JOURNAL; SINUS NODE; STRUCTURE ACTIVITY RELATION;

AMINO ACID SEQUENCE; ANIMALS; CADMIUM CHLORIDE; CYCLIC NUCLEOTIDE-GATED CATION CHANNELS; CYSTEINE; DITHIOTHREITOL; ETHYL METHANESULFONATE; FEMALE; ION CHANNEL GATING; KINETICS; MEMBRANE POTENTIALS; MICE; MICROINJECTIONS; MODELS, MOLECULAR; MOLECULAR SEQUENCE DATA; MUTATION; OOCYTES; PERMEABILITY; POTASSIUM CHANNELS; PROTEIN CONFORMATION; PROTEIN STRUCTURE, TERTIARY; REDUCING AGENTS; STRUCTURE-ACTIVITY RELATIONSHIP; SULFHYDRYL COMPOUNDS; SULFHYDRYL REAGENTS; XENOPUS LAEVIS;

EID: 38349145565     PISSN: 03636143     EISSN: 15221563     Source Type: Journal    
DOI: 10.1152/ajpcell.00340.2007     Document Type: Article

References (32)

1. Azene EM, Sang D, Tsang SY, Li RA. Pore-to-gate coupling of HCN channels revealed by a pore variant that contributes to gating but not permeation. Biochem Biophys Res Commun 327: 1131-1142, 2005.
2. Azene EM, Xue T, Li RA. Molecular basis of the effect of potassium on heterologously expressed pacemaker (HCN) channels. J Physiol 547: 349-356, 2003.
3. Becchetti A, Gamel K. The properties of cysteine mutants in the pore region of cyclic-nucleotide-gated channels. Pflügers Arch 438: 587-596, 1999.
4. Becchetti A, Gamel K, Torre V. Cyclic nucleotide-gated channels. Pore topology studied through the accessibility of reporter cysteines. J Gen Physiol 114: 377-392, 1999.
5. Bell DC, Yao H, Saenger RC, Riley JH, Siegelbaum SA. Changes in local S4 environment provide a voltage-sensing mechanism for mammalian hyperpolarization-activated HCN channels. J Gen Physiol 123: 5-19, 2004.
6. Brown HF, Giles W, Noble SJ. Membrane currents underlying activity in frog sinus venosus. J Physiol 271: 783-816, 1977.
7. Bucossi G, Nizzari M, Torre V. Single-channel properties of ionic channels gated by cyclic nucleotides. Biophys J 72: 1165-1181, 1997.
8. Chen S, Wang J, Siegelbaum SA. Properties of hyperpolarization- activated pacemaker current defined by coassembly of HCN1 and HCN2 subunits and basal modulation by cyclic nucleotide. J Gen Physiol 117: 491-504, 2001.
9. Creighton TE. Protein Folding. New York: Freeman, 1992.
10. DiFrancesco D. A new interpretation of the pace-maker current in calf Purkinje fibres. J Physiol 314: 359-376, 1981.
11. DiFrancesco D. Pacemaker mechanisms in cardiac tissue. Annu Rev Physiol 55: 455-472, 1993.
12. DiFrancesco D. A study of the ionic nature of the pace-maker current in calf Purkinje fibres. J Physiol 314: 377-393, 1981.
13. Doyle DA, Morais Cabral J, Pfuetzner RA, Kuo A, Gulbis JM, Cohen SL, Chait BT, MacKinnon R. The structure of the potassium channel: molecular basis of K+ conduction and selectivity. Science 280: 69-77, 1998.
14. Er F, Larbig R, Ludwig A, Biel M, Hofmann F, Beuckelmann DJ, Hoppe UC. Dominant-negative suppression of HCN channels markedly reduces the native pacemaker current If and undermines spontaneous beating of neonatal cardiomyocytes. Circulation 107: 485-489, 2003.
15. Flynn GE, Zagotta WN. Conformational changes in S6 coupled to the opening of cyclic nucleotide-gated channels. Neuron 30: 689-698, 2001.
16. Gauss R, Seifert R, Kaupp UB. Molecular identification of a hyperpolarization-activated channel in sea urchin sperm. Nature 393: 583-587, 1998.
17. 2+ blockage, and permeation of olfactory cyclic nucleotide-gated channels. J Gen Physiol 116: 311-326, 2000.
18. Hille B. Ionic Channels of Excitable Membranes. Sunderland, MA: Sinauer, 2002.
19. Kaupp UB, Seifert R. Cyclic nucleotide-gated ion channels. Physiol Rev 82: 769-824, 2002.
20. Ludwig A, Zong X, Jeglitsch M, Hofmann F, Biel M. A family of hyperpolarization-activated mammalian cation channels. Nature 393: 587-591, 1998.
21. Pape HC. Queer current and pacemaker: the hyperpolarization- activated cation current in neurons. Annu Rev Physiol 58: 299-327, 1996.
22. Prole DL, Yellen G. Reversal of HCN channel voltage dependence via bridging of the S4-S5 linker and post-S6. J Gen Physiol 128: 273-282, 2006.
23. Root MJ, MacKinnon R. Identification of an external divalent cation-binding site in the pore of a cGMP-activated channel. Neuron 11: 459-466, 1993.
24. Santoro B, Chen S, Luthi A, Pavlidis P, Shumyatsky GP, Tibbs GR, Siegelbaum SA. Molecular and functional heterogeneity of hyperpolarization-activated pacemaker channels in the mouse CNS. J Neurosci 20: 5264-5275, 2000.
25. Santoro B, Liu DT, Yao H, Bartsch D, Kandel ER, Siegelbaum SA, Tibbs GR. Identification of a gene encoding a hyperpolarization-activated pacemaker channel of brain. Cell 93: 717-729, 1998.
26. Santoro B, Tibbs GR. The HCN gene family: molecular basis of the hyperpolarization-activated pacemaker channels. Ann NY Acad Sci 868: 741-764, 1999.
27. Siu CW, Lieu DK, Li RA. HCN-encoded pacemaker channels: from physiology and biophysics to bioengineering. J Membr Biol 214: 115-122, 2006.
28. Ulens C, Tytgat J. Functional heteromerization of HCN1 and HCN2 pacemaker channels. J Biol Chem 276: 6069-6072, 2001.
29. Wahl-Schott C, Baumann L, Zong X, Biel M. An arginine residue in the pore region is a key determinant of chloride dependence in cardiac pacemaker channels. J Biol Chem 280: 13694-13700, 2005.
30. Xue T, Li RA. An external determinant in the S5-P linker of the pacemaker (HCN) channel identified by sulfhydryl modification. J Biol Chem 277: 46233-46242, 2002.
31. Xue T, Marban E, Li RA. Dominant-negative suppression of HCN1- and HCN2-encoded pacemaker currents by an engineered HCN1 construct: insights into structure-function relationships and multimerization. Circ Res 90: 1267-1273, 2002.
32. Yanagihara K, Irisawa H. Potassium current during the pacemaker depolarization in rabbit sinoatrial node cell. Pflügers Arch 388: 255-260, 1980.