| Interaction between organism and the outside world is based on the structure of the nervous system, the information is transfered in the form of action potential on nerve, but how the nervous system distinguish action potential to identify different information and how to integrate and characterize the information is remain unknow, which has been a problem in the field of neuroscience, peope have successively proposed the concept of coding by pulse frequency and coding by rhythm, density of neural firing of action potentials and the interspike interval of action potentials has a wealth of implied information.Dynamic changes in the external information affect firing parameters, causing dynamic changes of firing pattern on nerve, the action potential actually results from ion channels in neurons such as sodium channel, calcium channel, potassium channel, so any factors that impact channel switch can affect the appearance and firing pattern of action potential, recent years, suggested by research in theoretical models, we make further studies in the area of peripheral injuried nerve and find many types of spontaneous discharge, for example, changing the extracellular calcium concentration, we find a great variety of firing patterns and pattern transitions;indicating calcium channels are involved in the regulation of neural discharge, and blocking potassium channels with TEA, it shows a similar simple firing pattern and pattern transition, showing three types of firing patterns transition modes from period 1 to period 2.Therefore, the potassium ion channel also plays a key role in regulation of firing pattern, TEA is the non-specific blocker, then which type of potassium ion channel is exately blocked when the firing pattern is changed by application of TEA? Is it calcium-activated potassium ion channel? Which is waiting for further studies. Calcium-activated potassium ion channel include the big conductance channel (BK), the intermediate conductance channel (IK), and small conductance channel (SK), IBTX is the specific blocker of BK channe, apamin is the specific blocker of SK channel.Based on the study of calcium chaninel, this experiment focuses on the research of potassium channels, especially the role of calcium-dependent potassium channels on firing pattern and bifurcation scenarios of firing, the paper mainly include the following three parts of the experiment:1.examine the effect of EGTA on spontaneous firing on injuried nerve model.2. observe the change of firing pattern caused by application of the non-specific potassium ion channel blocker TEA;3. examine the effect of relatively specific calcium-dependent potassium channel blocker IBTX and apamin on spontaneous firing on injuried nerve model, then carefully compare the effect of non-specific blocker and the specific blocker. the study provide evidence to the fact that calcium-dependent potassium channels are involved in the injured nerves of CCI model, and plays an important role in generation and regulation of spontaneous firing on injured nerves.these findings help to understand the mechanism of chronic peripheral neuropathic pain, and also provides a new way for clinical treatment of chronic neuropathic pain.The main results are as follows:1.observe the change of firing pattern in injury nerve after application of calcium channel blocker EGTA, with the decreasing of Ca2+, the neural firing was increased and several firing pattern transitions were observed, such as adding-bifurcation, doubling-bifurcation.2.the firing patterns can be changed by the application of potassium channel blocker TEA, In the experimental pacemaker, the non-specific potassium channel blocker TEA would cause firing frequency increase significantly, and also many different firing patterns appeared, include periodic rhythm with intermittency, bursting, spiking, chaotic bursting, chaotic bursting, chaotic spiking, and the coexistence of many types of periodic firing pattern, integer multiple bursting, new firing pattern between period 1 bursting and period 2 bursting and new firing pattern between period 2 bursting and period 3 bursting, also bifurcation scenarios of firings such as bursting including a bifurcation scenario from period 1 bursting to period 1 spiking directly, a bifurcation scenario from period 1 to period 1 spiking via period 2 bursting, some of the transitions was via period-doubling bifurcation, and some via period-adding bifurcation. A complex and a complete rhythm transitions patterns also observed in the TEA solution, however it is difficult to find only period 4 bursting, period 5 bursting etc.3.Observe the effect of specific calcium-dependent potassium channels on firing pattern by application the specific BK channel blocker IBTX, SK channel blocker apamin, and we find:1, both IBTX and apamin could increase the firing frequency, but much less than the degree caused by TEA; 2, both IBTX and apamin could lead to bifurcation scenarios of firings, resulting in a part of bifurcation process induced by TEA and the bifurcation transition process induced by combination of IBTX and apamin is more similar to the TEA-induced one; 3, the bifurcation scenarios of firings after application of IBTX, apamin or TEA is siminar but showing mini difference, these results provide evidence to the fact that calcium-dependent potassium channels are involved in the injured nerves of CCI model, indicating BK and SK channels may exist in CCI model, and play different roles in regulating the firing pattern.4.In the process that the firing patterns are changed by the application of potassium channel blockers, I find many types of bursting transitions among 2 states and bursting transitions among 3 states.(a), bursting transitions among 2 states, for example, bursting transitions among period 1 and period 2; bursting transitions among period 2 and period 3, and each have a variety of firing forms and forms of return map; (b), bursting transitions among 3 states, for example, bursting transitions among quiescence, period 1 and period 2; bursting transitions among quiescence, period 2 and period 3, bursting transitions among quiescence, period 1 and high order periodic bursting; bursting transitions among quiescence, period 2 and chaos, bursting transitions among quiescence, period 1 and chaos, bursting transitions among quiescence, period 1, period 2, period 3 period 4 and period 5, and each have a variety of firing forms and forms of return map;(c), a bifurcation scenario when washed after application of TEA, find transitions between two adjacent periods is via bursting transitions among 2 states and bursting transitions among 3 states.The results show that changes in extracellular calcium and potassium channel blockers concentration could change firing frenquency and firing pattern, and could lead to many types of bifurcation transition process, and BK, SK play key roles, which is the basis for further study of the different activation kinetics of BK, SK channels. |
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