Study On Characteristics Of HCN Channels By Electrical Stimulation

Since HCN channel has been discovered, its special property of hyperpolarization activated immediately caused the attention of the scientific researchers. HCN channel has involved in many neural activity, including regulating the rhythm and the neurons activities dendritic integration, controlling the resting membrane potential of cells and synaptic transmission, etc. In recent years, many researchers studied the mechanism of epileptic disease by synaptic NMDA and GABAA receptors and the amino acid neurotransmitter receptors outside, to explore the role of HCN channels in epilepsy disease. At the same time, there are also some studies have shown that the abnormal regulation of HCN channel may be associated with many diseases in the nervous system, s u c h a s e p i l e p s y, n e u r o p a t h i c p a i n, P a r k i n s o n ' s d i s e a s e, a n d s o o n.In order to study the characteristics of HCN channel by electrical stimulation, we simulated the epileptic discharge by electric stimulation experiments to study on the distribution of HCN channel, the channel characteristics and molecular mechanism. In the study, we used immunofluorescence technology to research the effect of electrical stimulation on the distribution of HCN channel in newborn rat hippocampal neurons, used cell patchclamp technique to study the influence of electrical stimulation on the open probability of HCN channel, and used ELISA kit to study electrical stimulation effect on the content of cAMP.The results showed that the distribution of HCN4 channel changed from cell bodies to dendrites of the neurons, and repeated electrical stimulation led to in crease the open probability of HCN single channel. Further study found that these changes might be due to the influence of cAMP, showing that the increasing content of cAMP in the cerebral cortex and decreasing open probability of HCN single channel by inhibiting the production of cAMP after electrical stimulation.The results above indicated that the electrical stimulation(simulated epileptic discharge) can affect the neural signal conduction velocity, characterized by the distribution of HCN channel on neurons being significantly changed. At the same time, it can increase the content of c AMP, and increase the open probability of HCN single channel. On the effect of conduction velocity and physiological property of HCN channel, a large number of neurons can participate in producing super synchronization discharge, which is one of the mechanisms of epilepsy. Our study simulated the process of epileptic discharge by electrical stimulation experiments can not only reveal the effect of electrical stimulation on the distribution and open probability of HCN channel, but also contribute to explain the mechanism of epileptic discharge.