Myelinated Ah-type trigeminal ganglion neurons in female rats: neuroexcitability, chemosensitivity to histamine, and potential clinical impact

• Published in: Neuroscience letters 2014-05, Vol.567, p.74-79
• Main Authors: Liu, Hua, Xin, Ting, He, Wei, Li, Fang, Su, Zhi-Qiang
• Format: Article
• Language: English
• Subjects: Action Potentials; Animals; Female; Histamine - pharmacology; Histamine - physiology; Ion channel; Large-Conductance Calcium-Activated Potassium Channels - physiology; Male; Myelin Sheath - metabolism; Myelination; Neuroexcitability; Patch-Clamp Techniques; Rats, Sprague-Dawley; Sensory Receptor Cells - physiology; Sex Factors; Trigeminal Ganglion - cytology; Trigeminal Ganglion - physiology; Trigeminal ganglion neuron; Voltage-Gated Sodium Channels - physiology; Whole-cell patch
• ISSN: 0304-3940; 1872-7972
• DOI: 10.1016/j.neulet.2014.03.039

Myelinated Ah-type trigeminal ganglion neurons are observed except for myelinated A- and unmyelinated C-types (upper left figures). These myelinated Ah-type trigeminal ganglion neurons highly respond to histamine (upper right figures). The myelinated Ah-type trigeminal ganglion neuron demonstrates higher neuroexcitability because of functional expression of persistent TTX-R Na+ channel currents (central panel figures) and large conductance Ca2+-activated-K+ channel currents (lower panel figures). •Myelinated Ah-type TGNs are gender-specifically distributed in females.•Ah-type TGNs show low firing threshold and high firing capability upon stimulation.•Ah-type TGNs express persistent TTX-R Na+, TTX-R Na+, and KCa1.1 channels.•Ah-type TGNs show more potent chemosensitivity to histamine.•Ah-type TGNs may play key roles in gender difference in prevalence of migraine. Migraine is a chronic neurological disorder characterized by recurrent moderate-to-severe headaches often associated with numerous autonomic nervous system symptoms, and it is more prevalent in women. To fully understand the underlying mechanism, standard electrophysiology was performed with trigeminal ganglion neurons (TGNs) isolated from adult rats of both genders using the whole-cell patch clamp technique to test the distribution, neuroexcitability, and chemosensitivity to histamine. In addition to traditionally classified A- and C-type TGNs, myelinated Ah-type TGNs were also observed in females. The electrophysiological features showed low firing threshold and the capability to fire repetitively upon stimulation. Ah-type neurons also functionally expressed persistent TTX-R Na+ channels with more hyperpolarized activating voltage. Iberiotoxin and NS11021 significantly altered the discharge profiles of Ah-type TGNs. Finally, Ah-type TGNs showed a more potent reaction to histamine, with relatively larger inward currents and membrane depolarization compared with C-types. These data provide evidence of the gender-specific distribution of myelinated Ah-type TGNs in adult female rats, characterized by a low threshold and high frequency of firing that are at least partially attributable to persistent TTX-R Na+ and BK-KCa channel expression and potent chemosensitivity to histamine, suggesting that Ah-type TGNs may play a key role in gender differences in migraine.