Background:Migraine is a debilitating neurological disorder involving abnormal trigeminovascular activation and sensitization. However, the underlying cellular and molecular mechanisms remain unclear.
Methods:A rat model of conscious migraine was established through the electrical stimulation (ES) of the dural mater surrounding the superior sagittal sinus. Using patch clamp recording, immunofluorescent labelling, enzyme-linked immunosorbent assays and western blot analysis, we studied the effects of ES on sensory neuronal excitability and elucidated the underlying mechanisms mediated by voltage-gated ion channels.
Results:The calcitonin gene-related peptide (CGRP) level in the jugular vein blood and the number of CGRP-positive neurons in the trigeminal ganglia (TGs) were significantly increased in rats with ES-induced migraine. The application of ES increased actional potential firing in both small-sized IB4-negative (IB4-) and IB4+ TG neurons. No significant changes in voltage-gated Na+ currents were observed in the ES-treated groups. ES robustly suppressed the transient outward K+ current (IA) in both types of TG neurons, while the delayed rectifier K+ current remained unchanged. Immunoblot analysis revealed that the protein expression of Kv4.3 was significantly decreased in the ES-treated groups, while Kv1.4 remained unaffected. Interestingly, ES increased the P/Q-type and T-type Ca2+ currents in small-sized IB4- TG neurons, while there were no significant changes in the IB4+ subpopulation of neurons.
Conclusion:These results suggest that ES decreases the IA in small-sized TG neurons and increases P/Q- and T-type Ca2+ currents in the IB4- subpopulation of TG neurons, which might contribute to neuronal hyperexcitability in a rat model of ES-induced migraine.
