title: Ca2+ permeation in cyclic nucleotide-gated channels.
abstract: Cyclic nucleotide-gated (CNG) channels conduct Na+, K+ and Ca2+ currents under the control of cGMP and cAMP. Activation of CNG channels leads to depolarization of the membrane voltage and to a concomitant increase of the cytosolic Ca2+ concentration. Several polypeptides were identified that constitute principal and modulatory subunits of CNG channels in both neurons and non-excitable cells, co-assembling to form a variety of heteromeric proteins with distinct biophysical properties. Since the contribution of each channel type to Ca2+ signaling depends on its specific Ca2+ conductance, it is necessary to analyze Ca2+ permeation for each individual channel type. We have analyzed Ca2+ permeation in all principal subunits of vertebrates and for a principal subunit from Drosophila melanogaster. We measured the fractional Ca2+ current over the physiological range of Ca2+ concentrations and found that Ca2+ permeation is determined by subunit composition and modulated by membrane voltage and extracellular pH. Ca2+ permeation is controlled by the Ca2+-binding affinity of the intrapore cation-binding site, which varies profoundly between members of the CNG channel family, and gives rise to a surprising diversity in the ability to generate Ca2+ signals.
authors.affiliation: Institut für Biologische Informationsverarbeitung, Forschungszentrum Jülich, 52425 Jülich.
authors.forename: C
authors.initials: C
authors.lastname: Dzeja
authors.forename: V
authors.initials: V
authors.lastname: Hagen
authors.forename: U B
authors.initials: UB
authors.lastname: Kaupp
authors.forename: S
authors.initials: S
authors.lastname: Frings
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism; D020013:Calcium Signaling; D002417:Cattle; D002460:Cell Line; D002463:Cell Membrane Permeability; D054815:Cyclic Nucleotide-Gated Cation Channels; D004331:Drosophila melanogaster; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D015640:Ion Channel Gating; D007473:Ion Channels / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D007700:Kinetics; D008564:Membrane Potentials; D009712:Nucleotides, Cyclic / Q000378:metabolism; D018034:Olfactory Receptor Neurons / Q000378:metabolism; D011487:Protein Conformation; D011817:Rabbits; D051381:Rats; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D014162:Transfection
chemical_list: D015220:Calcium Channels; D054815:Cyclic Nucleotide-Gated Cation Channels; D007473:Ion Channels; D009712:Nucleotides, Cyclic; D011994:Recombinant Proteins; D002118:Calcium