The Research Of Ion Channel In Nitroglycerin Induced Migraine Model

BACKROUNDSMigraine is a vascular-neurological headache characterized by chronicity and relapsing, which presents with monolateral or bilateral impulsive headache. The attack of migraine in China tends to increase and be younger year by year; in addition the recurrent headache will decrease the qualities in work and life.The etiopathogenisis and mechanism of migraine are not clear, which of multiple factors lead to the complexity and diversity of its physiopathology. The recent studies showed the onset of familial hemiplegic migraine is correlated with the polymorphism of some certain ion channel gene. In 1996, Ophoff and his colleagues discovered and clone the virulence gene in FHM1, which is so-called CACNA1A gene. Ddfusco and his intimates detected the point mutation in ATP1A2 gene, which encode P-type Na+/K+ ATPase and is regarded as the virulence gene of FHM2. D Dichgans and his workers found the mutation of SCN1A may lead to the attack of FHM3.Is ion channel a certain components in the physiopathology of migraine? Is the mechanism of ion channel related with other hypothesis of migraine? The clinical experience in migraine therapy may give us some instructions. Patients can benefit from the preventive therapy with calcium agonist and sodium inhibitors such as verapamil, flunarizine, lamotrigine and carbamazepine. On the basis of the correlation between ion channel and FHM and the therapy by ion channel associated drugs, we conjecture the ion channel may participate in the mechanism of migraine.ObjectionsTo make the Nitroglycerin induced experimental migraine model, and to investigate the possible mechanisms of P-type Na+/K+ ATPase, Nav1.1 and Cav1.1 in the procession of migraine.Methods1. Grouping: 20 Sprague-Dawley (SD) rattus were divided into two randomized groups, which were called model group and NS control group.2. Building NTG induced migraine model: NTG was injected subcutaneouly by 10 mg/kg, 1 time every week for 4 weeks.3. The expression of mRNA of P-type Na+/K+ ATPase, Cav2.1 and Nav1.1 in cerebrum, trigeminal ganglion and brain stem were detected by RT-PCR.4. The expression of protein of P-type Na+/K+ ATPase, Cav2.1 and Nav1.1 in cerebrum, trigeminal ganglion and brain stem were investigated by Western-blotting.5. The activity of P-type Na+/K+ ATPase in cerebrum, trigeminal ganglion and brain stem were detected by immuno-precipitation.6. The concentration of intracellular Ca++ in cerebrum, trigeminal ganglion and brain stem were detected by immunofluorescence.Results1. Comparing with control group, the expression of mRNA and protein and the activity of P-type Na+/K+ ATPase in cerebrum, trigeminal ganglion and brain stem were all downregulated (p<0.05) .2. Comparing with control group, the expression of mRNA and protein of Cav2.1 and the concentration of intracellular Ca++ in cerebrum, trigeminal ganglion and brain stem were all upregulated (p<0.05) .3. There is no statistical difference (p>0.05) between model group and NS control group in the expression of mRNA and protein of Nav1.1 of cerebrum, trigeminal ganglion and brain stem.Conclusions1. P-type Na+/K+ ATPase and Cav2.1 may infect the pathogenesis of migraine by their expression (/ and activity).2. The expression of Nav1.1 may have nothing to do with the pathophysiological processes of migraine.