Electrical stimulation of the superior sagittal sinus suppresses A-type K(+) currents and increases P/Q- and T-type Ca(2+) currents in rat trigeminal ganglion neurons

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 IB(4)-negative (IB(4)(−)) and IB(4)(+) 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 (I(A)) 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 Ca(2+) currents in small-sized IB(4)(−) TG neurons, while there were no significant changes in the IB(4)(+) subpopulation of neurons. CONCLUSION: These results suggest that ES decreases the I(A) in small-sized TG neurons and increases P/Q- and T-type Ca(2+) currents in the IB(4)(−) subpopulation of TG neurons, which might contribute to neuronal hyperexcitability in a rat model of ES-induced migraine.