Frenz CT, Hansen A, Dupuis ND, Shultz N, Levinson SR, Finger TE, Dionne VE. Na V 1.5 sodium channel window currents contribute to spontaneous firing in olfactory sensory neurons. J Neurophysiol 112: 1091-1104. First published May 28, 2014 doi:10.1152/jn.00154.2014.-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 ϩ channels in OSNs to assess their role in spontaneous activity. Whole cell patchclamp recordings from OSNs demonstrated both tetrodotoxin-sensitive and tetrodotoxin-resistant components of Na ϩ current. RT-PCR showed mRNAs for five of the nine different Na ϩ channel ␣-subunits in olfactory tissue; only one was tetrodotoxin resistant, the so-called cardiac subtype Na V 1.5. Immunohistochemical analysis indicated that Na V 1.5 is present in the apical knob of OSN dendrites but not in the axon. The Na V 1.5 channels in OSNs exhibited two important features: 1) a half-inactivation potential near Ϫ100 mV, well below the resting potential, and 2) a window current centered near the resting potential. The negative half-inactivation potential renders most Na V 1.5 channels in OSNs inactivated at the resting potential, while the window current indicates that the minor fraction of noninactivated Na V 1.5 channels have a small probability of opening spontaneously at the resting potential. When the tetrodotoxin-sensitive Na ϩ channels were blocked by nanomolar tetrodotoxin at the resting potential, spontaneous firing was suppressed as expected. Furthermore, selectively blocking Na V 1.5 channels with Zn 2ϩ in the absence of tetrodotoxin also suppressed spontaneous firing, indicating that Na V 1.5 channels are required for spontaneous activity despite resting inactivation. We propose that window currents produced by noninactivated Na V 1.5 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 ϩ channel subtypes.