# Immature olfactory sensory neurons are intrinsically excitable and show maturation-dependent changes in voltage-gated Na+ and K+ currents

**Authors:** Chiara Ricci, Cesar Adolfo Sánchez Triviño, Uday Rangaswamy, Lorenza Tortella, Remo Sanges, Anna Boccaccio, Anna Menini

PMC · DOI: 10.1007/s00424-026-03159-y · Pflugers Archiv · 2026-03-06

## TL;DR

This study reveals how immature olfactory neurons differ in electrical activity from mature ones, shedding light on their role in odor processing.

## Contribution

The study identifies maturation-dependent changes in voltage-gated ion currents in olfactory sensory neurons.

## Key findings

- Immature OSNs show spontaneous firing at lower frequencies and have distinct electrical properties compared to mature neurons.
- Voltage-gated Na⁺ and K⁺ currents in immature OSNs differ significantly from those in mature OSNs.
- Transcriptomic data align with functional changes, showing upregulation of ion channel genes during maturation.

## Abstract

Olfactory sensory neurons (OSNs) detect odorants and send electrical signals to glomeruli in the olfactory bulb. Unlike most neurons, OSNs are continuously regenerated throughout life and immature neurons contribute to odorant-evoked responses in glomeruli. However, their intrinsic excitability properties are largely unknown. Here, we used acute slices of the olfactory epithelium from neonatal OMP-GFP mice to visually identify mature and immature OSNs and performed patch-clamp recordings to investigate their functional properties. Loose-patch recordings showed that immature OSNs display spontaneous firing at lower frequency than mature neurons. Whole-cell recordings showed that immature OSNs have more depolarized resting potentials, higher input resistance, fire only with phasic patterns, and generate slower action potentials with more depolarized thresholds. Instead, mature OSNs exhibited both phasic and tonic repetitive firing and faster spike kinetics. Voltage-clamp experiments showed that voltage-gated Na⁺ currents in immature OSNs were almost entirely TTX-sensitive, whereas mature OSNs had both TTX-sensitive and TTX-resistant components whose availability depends on membrane potential. Voltage-gated K⁺ currents also differed with maturation: immature OSNs lacked a transient component and had only a sustained K⁺ current, whereas mature OSNs displayed both a transient component and an increased sustained current. Analysis of single-cell transcriptomic data identified upregulation of some Na⁺ and K⁺ channel genes during OSN maturation, consistent with the functional changes. Together, these results provide insights into the intrinsic excitability of immature OSNs and show how intrinsic properties change as OSNs mature, providing a foundation for future studies on the role of immature OSNs in sensory processing.

The online version contains supplementary material available at 10.1007/s00424-026-03159-y.

## Linked entities

- **Chemicals:** TTX (PubChem CID 4490623)
- **Species:** Mus musculus (taxon 10090)

## Full-text entities

- **Genes:** Adcy3 (adenylate cyclase 3) [NCBI Gene 104111] {aka AC3, ACIII, mKIAA0511}, Kcnc1 (potassium voltage gated channel, Shaw-related subfamily, member 1) [NCBI Gene 16502] {aka C230009H10Rik, KShIIIB, KV4, Kcr2-1, Kv3.1, NGK2}, Gnal (guanine nucleotide binding protein, alpha stimulating, olfactory type) [NCBI Gene 14680] {aka 2610011C15Rik, 9630020G10Rik, Galphaolf, Gna10, Golf, Hg1o}, Kcna2 (potassium voltage-gated channel, shaker-related subfamily, member 2) [NCBI Gene 16490] {aka Akr6a4, Gm10672, Kca1-2, Kv1.2, Mk-2}, Car2 (carbonic anhydrase 2) [NCBI Gene 12349] {aka CAII, Ca2, Car-2, Ltw-5, Lvtw-5}, Bhlhe23 (basic helix-loop-helix family, member e23) [NCBI Gene 140489] {aka A930001L02Rik, BETA4, Beta3b, Bhlhb4}, Scn3a (sodium channel, voltage-gated, type III, alpha) [NCBI Gene 20269] {aka Gm1000, Nav1.3}, Gap43 (growth associated protein 43) [NCBI Gene 14432] {aka B-50, Basp2, GAP-43}, Kcna5 (potassium voltage-gated channel, shaker-related subfamily, member 5) [NCBI Gene 16493] {aka Kv1.5}, Oprm1 (opioid receptor, mu 1) [NCBI Gene 18390] {aka M-OR-1, MOP-R, MOR-1, MOR-1O, Oprm, mor}, Kcnd3 (potassium voltage-gated channel, Shal-related family, member 3) [NCBI Gene 56543] {aka Kncd3, Kv4.3}, Kcnd2 (potassium voltage-gated channel, Shal-related family, member 2) [NCBI Gene 16508] {aka Gm52855, Kv4.2}, Scn4b (sodium channel, type IV, beta) [NCBI Gene 399548] {aka Gm1471}, Kcnd1 (potassium voltage-gated channel, Shal-related family, member 1) [NCBI Gene 16506] {aka 1110037K09Rik, Kca2-1, Kv4.1, Shal, Shal1, mShal1}, Scn8a (sodium channel, voltage-gated, type VIII, alpha) [NCBI Gene 20273] {aka C630029C19Rik, NaCh6, Nav1.6, dmu, med, mnd-2}, Gng8 (guanine nucleotide binding protein (G protein), gamma 8) [NCBI Gene 14709] {aka G(y)8, Hg3e}, Kcna6 (potassium voltage-gated channel, shaker-related, subfamily, member 6) [NCBI Gene 16494] {aka Kv1.6, MK1.6}, Kcna4 (potassium voltage-gated channel, shaker-related subfamily, member 4) [NCBI Gene 16492] {aka Kv1.4}, Kcnc4 (potassium voltage gated channel, Shaw-related subfamily, member 4) [NCBI Gene 99738] {aka KSHIIIC, Kcr2-4, Kv3.4}, Omp (olfactory marker protein) [NCBI Gene 18378], Gngt2 (guanine nucleotide binding protein (G protein), gamma transducing activity polypeptide 2) [NCBI Gene 14710] {aka Hg3i}, Kcnb1 (potassium voltage gated channel, Shab-related subfamily, member 1) [NCBI Gene 16500] {aka Kcr1-1, Kv2.1, Shab}, Scn2a (sodium channel, voltage-gated, type II, alpha) [NCBI Gene 110876] {aka 6430408L10, A230052E19Rik, Nav1.2, Scn2a1}, Scn5a (sodium channel, voltage-gated, type V, alpha) [NCBI Gene 20271] {aka Nav1.5, Nav1.5c, SkM1, SkM2, mH1}, Or7a (olfactory receptor 7A complex) [NCBI Gene 18371] {aka M71, MOR171-2, Olfr7}, Ces1e (carboxylesterase 1E) [NCBI Gene 13897] {aka Eg, Es-22, Es22, egasyn}, Ano2 (anoctamin 2) [NCBI Gene 243634] {aka Tmem16b}, Scn9a (sodium channel, voltage-gated, type IX, alpha) [NCBI Gene 20274] {aka Nav1.7, PN1, mKIAA4197}, Scn3b (sodium channel, voltage-gated, type III, beta) [NCBI Gene 235281] {aka 1110001K16Rik, 4833414B02Rik, Scnb3}
- **Diseases:** OSNs (MESH:D000857)
- **Chemicals:** NaOH (MESH:D012972), CdCl2 (MESH:D019256), glucose (MESH:D005947), DAPI (MESH:C007293), KCl (MESH:D011189), CaCl2 (MESH:D002122), Tween-20 (MESH:D011136), silver (MESH:D012834), KOH (MESH:C029943), Agarose (MESH:D012685), PFA (MESH:C003043), EGTA (MESH:D004533), Cs+ (MESH:D002586), MgATP (MESH:D000255), water (MESH:D014867), CsCl (MESH:C028019), agar (MESH:D000362), MgSO4 (MESH:D008278), Na+ (MESH:D012964), HEPES (MESH:D006531), K+ (MESH:D011188), 4-AP (MESH:D015761), NaCl (MESH:D012965), NaHCO3 (MESH:D017693), ACSF (-)
- **Species:** Homo sapiens (human, species) [taxon 9606], Mus musculus (house mouse, species) [taxon 10090]
- **Cell lines:** /6 — Homo sapiens (Human), Tongue squamous cell carcinoma, Cancer cell line (CVCL_5985), C57BL/6 — Mus musculus (Mouse), Transformed cell line (CVCL_C0MU)

## Full text

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## Figures

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Source: https://tomesphere.com/paper/PMC12963238