| The mechanism of general anesthetics is an important part of anesthesiolo-gy. But the exact mechanism of general anesthetics is unclear. In general, the mechanism of inhaled anesthetics is more complex than that of intravenous general anesthetics. Some scholar thought the mechanism of intravenous anesthetics might be partly the same as that of inhaled anesthetics. No matter where general anesthetics act in macroscopic and microscopic anatomic level, it is certain that the position general anesthetics act on is on the nerve membrane in molecular level and increasing evidence had indicated that anesthetics set their sites on ion channels.Over the past years, the two receptor - gated ion channels of nicotinic acetycholine (nACh) and -y - aminobutyric acid (GAB A) had been widely studied in so many ion channels. But the results were different because of the differences in experimental protocols and doses of general anesthetics. Generally speaking, nACh receptor channels are not the main targets of anesthetic action. Although GABAA receptor channels are commonly considered as one of the main targets the general anesthetics act on, the results could not explain all the phenomenon of general anesthesia. Therefore, much attention has been paid to other excitatory ion channels recently. Sodium channels, which play an important part in the production of action potential and the conduction of nerve pulse, are onekind of the main excitatory voltage - gated ion channels and have been proposed as possible anesthetic targets once more because of many new experimental evidences.The aim of the present research is to investigate the effects of general anesthetics (propofol and isoflurane) and local anesthetics (Lidocaine) on the sodium channel currents of brain in rats.Part One Effects of Propofol on the Sodium Channel Currents of Hippocampal Pyramidal Neurons in RatsMaterials and MethodsSD rats aged 10 ~ 14 days, male and female, weighed from 20 ~30 grams. Heads sheared, Hippocampus were detached and put into 0 ~4TI artificial cerebral spinal fluid (ACSF) . Then they were cut into 500 jxm thick brain slices . The slices were put into incubate chamber full of ACSF and the fluid were saturated by mixed gas of 95% 02 and 5% C02 to maintain the pH at 7. 35 ~ 7.40 for Ih. 0.05%Trypsin and 0.05% Pronase were administered into the chamber one after another to yield enzymolysis ( 30 min , 32癈 ). One of the hippocampus slice was gently transferred into a piece of glasses full of 1ml ACSF, lightly blown with two Pasteru straws which were given heat treatment and whose diameters were 400fjun and 150{jutn, and then filtered into perfusion chamber fixed on an inverted microscope. The whole - cell patch clamp record began after 15 ~ 20min and perfusion 3 times with extracellular fluid.Sodium currents were recorded using the whole - cell configuration of the patch - clamp recording technique, using a standard patch - clamp amplifier (EPC - 9, HEKA, German) controlled by commercially available software (pulse8.02) on a standard personal computer. Currents were digitized and recorded to hard disk.According to the concentrations( uM) of propofol (Pro) and correspondentconcentrations of intralipid (ILP) , the study was divided into 7 groups, which were Pro10, Pro30, Pro50, Pro100, ILP50, ILP100 and Control group. Each group contained 6 cells, and the sodium channel currents were recorded before drug administration, 2 min after administration and 2 min after washout, respectively. Suppression was calculated as the reduction of the maximum inward current, expressed as percentage of control.ResultsThe peak sodium currents of the Con group, ILP50 and ILP100 were de-creasedby4.2 ±3.2% ,5.7 ±4. 6%and4. 3 ±3. 1% , respectively ( P > 0.05) ;Propofol showed a concentration -relative effect on the peak sodium current suppression( r = 0. 993, P <0. 01) , the suppression rates of Pro10, Pro30, Pro50and Pro100werel4.4±8.7%(P<0.05) ,43. 2 ±8. 8% ( P <0. 01 ) , 67.2±18.1%(P<0.01)and 85.1±14.9%(P<0.01, respect...
|
PDF Full Text Request