The Research Of Small Conductance Calcium-activated Potassium Channel SK3 Expression In Rat Migraine Model

Migraine is a common disease in the nervous system which badly affects the patient' s life and work quality. At present the etiopathogenisis of migraine remains elusive. Brainstem may be the potential migraine "generator" region, then migraine may be origined from the nervous excitation of some brainstem nucleus (including serotonergic neuron). The recent studies of the polymorphism of some ion channel gene in the linkage of familial hemiplegic migraine reveal that migraine may be have correlation with ion channels. Some research demostrate that the polymorphic poly-glutamine stretch CAG of coding gene KCNN3 of small conductance calcium-activated potassium channel SK3 is relate to common migraine. SK3 displays in the brainstem fully, its variety can affect the monoaminergic transmitter release remarkly, for example 5-HT, DA, and et al. SK3 channel activation can generate the medium afterhyperpolarization (mAHP), alternate the firing pattern of the neurons, take part in the early stage of spike-frequency adaption and limit the firing frequency of action potentials. It is essential for normal neurotransmission, and has a close correlation with neuron excitability.ObjectiveTo discuss the correlation between small conductance calcium-activated potassium channel SK3 and migraine, and provide experimental foundation for researching pathogenesis of migraine and new treatment.Methods1. 56 adualt female Sprague-Dawley (SD) rattus are equally divided into four random groups, which are called control group(n=8), model group(n=16), flunarizine group(n=16) and carbamazepine group(n=16). The last three groups are divided into two random groups again, named the attacking group and intermittion group, and each group has eight rattus.2. The rattus in the model group, flunarizine group and carbamazepine group are injected nitroglycerin(10mg/kg) subcutaneously on back, one time every week, last for 5 weeks. Control group is injected NS instead. Flunarizine group and carbamazepine group are given flunarizine (5mg/kg) or carbamazepine (4mg/kg) respectively one time each day after the second injection. Model group are given NS (10ml/kg) one time each day after the second injection.3. All attacking groups are beheaded to take brainstem in the third hour after the fifth injection, and intermittion groups in the forth day after the fifth injection.4. The expression levels of small conductance calcium-activated potassium channel SK3 mRNA of brainstem are tested by RT-PCR. The expression levels of small conductance calcium-activated potassium channel SK3 protein of brainstem are tested by Western-blotting.Results1 .Comparing with control group, the expression levels of brainstem SK3 mRNA and protein in all the other groups are reduced (p<0.05).2.Comparing with intermittion group, the expression levels of brainstem SK3 mRNA and protein in corresponding attacking group are also reduced (p<0.05).3.Comparing with model group, there is no statistical difference in the expression levels of brainstem SK3 mRNA and protein in flunarizine group and carbamazepine group (p>0.05).Conclusions1.The expression levels of small conductance calcium-activated potassium channel SK3 reduction in brainstem may be have a correlation with the pathophysiology of migraine.2.Flunarizine and carbamazepine mechanism used for preventing migraine may be not realized by affecting the expression levels of SK3 mRNA and protein in brainstem.