Sensory Perception

One Channel for Pain and Smell

Science Signaling  19 Apr 2011:
Vol. 4, Issue 169, pp. ec106
DOI: 10.1126/scisignal.4169ec106

Mutations that inactivate the sodium channel Nav1.7, which is encoded by the SCN9A gene, cause channelopathy-associated insensitivity to pain (see Waxman). Weiss et al. examined three patients who had congenital analgesia and in whom loss-of-function mutations in SCN9A had been confirmed and found that these patients also failed to detect any of 40 test odors. Transcript and protein immunofluorescence analysis of human olfactory epithelium showed that Nav1.7 was present in olfactory sensory neurons (OSNs). To explore the mechanistic basis for the loss of smell, the authors engineered tissue-specific knockout mice lacking Nav1.7 in olfactory cells, including OSNs. Knockout pups were smaller in weight due to an apparent deficiency in eating, adult mice failed to respond to either attractive or repulsive odors, and female adults failed to retrieve pups that had been removed from the nest, which is a task that relies on smelling the missing pups. Although biophysical analysis of olfactory epithelial slices showed that the OSNs of the knockout mice exhibited normal initiation of action potentials in response to step depolarization or to odor application, the postsynaptic response [from OSNs to mitral/tufted (M/T) neurons] to stimulation was lacking in the knockout mice. Electrophysiological analysis and the fact that Nav1.7 was only present in the OSNs, not in the M/T cells, in wild-type animals indicated that the defect in the knockout mice was presynaptic. Thus, Nav1.7 loss of function disrupts not only pain signaling but also odor perception, producing two sensory deficiencies.

J. Weiss, M. Pyrski, E. Jacobi, B. Bufe, V. Willnecker, B. Schick, P. Zizzari, S. J. Gossage, C. A. Greer, T. Leinders-Zufall, C. G. Woods, J. N. Wood, F. Zufall, Loss-of-function mutations in sodium channel Nav1.7 cause anosmia. Nature 472, 186–190 (2011). [PubMed]

S. G. Waxman, Channelopathies have many faces. Nature 472, 173–174 (2011). [PubMed]