EXPRESS: Piezo1-mediated neuroexcitation via collaboration with KCa1.1 and Nav1.9 currents in myelinated Ah-type of trigeminal ganglion neurons in rats: mechanistic insights with sex-specific effects

Introduction: It has well been documented that sex-related difference in the prevalence of migraine is widely accepted with more commonly seen in female patients. Although trigeminal ganglion (TG) neurons are the key players in the etiology of migraine, the underlying pathophysiology remains under debate so far.

Methods: Myelinated Ah-type TG neurons were identified by the waveform characters of action potential (AP) conjugated with pharmacological validation using whole-cell patch techniques.

Results: The results showed that AP duration and current derivative for repolarization were markedly increased by 3 μM Yoda1 along with the increased firing frequency of repetitive discharge that could be abolished by 3 μM GsMTx4. Although Yoda1 concentration-dependently increased the peaks of Ca2+ currents, the blocker for Ca2+ channel ω-Conotoxin did not alter the AP waveform characters and discharge profiles, whereas Yoda1-mediated changes in AP waveform trajectory and repetitive discharge could be completely reversed by1.0 μM Iberiotoxin, a selective KCa1.1 blocker, suggesting that Piezo1-induced Ca2+ influx can activate KCa1.1 via presumably channel coupling. Additionally, Ah-type TG neurons functionally expressed Nav1.9/Nav1.8 in all tested neurons and their peaks were significantly increased by 3 μM Yoda1 and completely blocked by 3 μM GsMTx4.

Conclusion: These datasets have demonstrated Piezo1-mediated neuroexcitation of female-specific subpopulation of myelinated Ah-type TG neurons due at least to the coupling between N-type Ca2+ channel and KCa1.1 and functional upregulation of Nav1.9, which uncovers an additional insights for higher incidence of migraine in woman.

Ion channel coupling; KCa1.1; Nav1.9; Neuroexcitation; Piezo1; Trigeminal ganglion neurons.