title: NaV1.5 sodium channel window currents contribute to spontaneous firing in olfactory sensory neurons.
abstract: Olfactory sensory neurons (OSNs) fire spontaneously as well as in response to odor; both forms of firing are physiologically important. We studied voltage-gated Na(+) channels in OSNs to assess their role in spontaneous activity. Whole cell patch-clamp recordings from OSNs demonstrated both tetrodotoxin-sensitive and tetrodotoxin-resistant components of Na(+) current. RT-PCR showed mRNAs for five of the nine different Na(+) channel α-subunits in olfactory tissue; only one was tetrodotoxin resistant, the so-called cardiac subtype NaV1.5. Immunohistochemical analysis indicated that NaV1.5 is present in the apical knob of OSN dendrites but not in the axon. The NaV1.5 channels in OSNs exhibited two important features: 1) a half-inactivation potential near -100 mV, well below the resting potential, and 2) a window current centered near the resting potential. The negative half-inactivation potential renders most NaV1.5 channels in OSNs inactivated at the resting potential, while the window current indicates that the minor fraction of noninactivated NaV1.5 channels have a small probability of opening spontaneously at the resting potential. When the tetrodotoxin-sensitive Na(+) channels were blocked by nanomolar tetrodotoxin at the resting potential, spontaneous firing was suppressed as expected. Furthermore, selectively blocking NaV1.5 channels with Zn(2+) in the absence of tetrodotoxin also suppressed spontaneous firing, indicating that NaV1.5 channels are required for spontaneous activity despite resting inactivation. We propose that window currents produced by noninactivated NaV1.5 channels are one source of the generator potentials that trigger spontaneous firing, while the upstroke and propagation of action potentials in OSNs are borne by the tetrodotoxin-sensitive Na(+) channel subtypes.
authors.affiliation: Department of Biology, Boston University, Boston, Massachusetts;
authors.forename: Christopher T
authors.initials: CT
authors.lastname: Frenz
authors.affiliation: Department of Cellular and Developmental Biology, Rocky Mountain Taste and Smell Center, University of Colorado School of Medicine, Anschutz Medical Center, Aurora, Colorado; and.
authors.forename: Anne
authors.initials: A
authors.lastname: Hansen
authors.affiliation: Department of Biology, Boston University, Boston, Massachusetts;
authors.forename: Nicholas D
authors.initials: ND
authors.lastname: Dupuis
authors.affiliation: Department of Cellular and Developmental Biology, Rocky Mountain Taste and Smell Center, University of Colorado School of Medicine, Anschutz Medical Center, Aurora, Colorado; and.
authors.forename: Nicole
authors.initials: N
authors.lastname: Shultz
authors.affiliation: Department of Physiology and Biophysics, University of Colorado School of Medicine, Anschutz Medical Center, Aurora, Colorado.
authors.forename: Simon R
authors.initials: SR
authors.lastname: Levinson
authors.affiliation: Department of Cellular and Developmental Biology, Rocky Mountain Taste and Smell Center, University of Colorado School of Medicine, Anschutz Medical Center, Aurora, Colorado; and.
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Finger
authors.affiliation: Department of Biology, Boston University, Boston, Massachusetts; vdionne@bu.edu.
authors.forename: Vincent E
authors.initials: VE
authors.lastname: Dionne
mesh_terms: D000200:Action Potentials / Q000502:physiology*; D000818:Animals; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D062554:NAV1.5 Voltage-Gated Sodium Channel / Q000378:metabolism / Q000502:physiology*; D009831:Olfactory Mucosa / Q000166:cytology / Q000294:innervation* / Q000378:metabolism; D011984:Sensory Receptor Cells / Q000502:physiology*
chemical_list: D062554:NAV1.5 Voltage-Gated Sodium Channel; C568321:Scn5a protein, mouse
keywords: NaV1.5 sodium channels; olfaction; olfactory sensory neurons; spontaneous firing; window currents