| The mechanism of action by which diverse anesthetics result in the state of general anesthesia has not been elucidated completely, despite the widespread research have shown so many mechanisms about it. Recently, our understanding has upgraded dramatically from unitary mechanism to complicated and mulriple mechanisms of action for general anesthetics, and the investigatation has developed from cell to molecular level. Both inhaled and intravenous anesthetics may act by either enhancing inhibitory ion channel protein activity or suppressing excitatory ion channel protein transmission in central neural system to educe anesthetic action. For example, most intravenous agents and the halogeno-inhaled agents could facilitate the inhibitory gamma-aminobutyric acid type A (GABAA) and glycine channels and depress the excitatory N-methyl-D-aspartate (NMDA) and nicotinic acetylcholine (nACh) receptors. Nitrous oxide and ketamine act primarily by blocking the excitatory NMDA and enhancing the opioidμreceptors.The spinal cord layerⅡ, also called substansia gelatinosa (SG), is one of the primary central nerval system receiving the noxious information from periphery. It including so many complex local circuits of neurotransmission, which take part in the regulation of the harmful signals. There is report that the spinal cord is the key position which determines the minimum alveolar anesthetic concentration (MAC) of inhaled anesthetics. So we can see that the spinal cord is one of the potential target of the anesthetics inhibiting the afference of the noxious stimulation. It may be the mechanism of anesthesia that anesthetics would either affect kinds of neurotransmitters release, excitatory or inhibitory, or have an influence on their receptors.Ketamine(KTM) which is an intravenous anesthetic agent used for induction and maintenance of anesthesia is a non-competitive NMDA receptor antagonist. Because of more effective analgesic effect than propofol or inhaled anesthetic agents, ketamine has been widely applied in patients especially for paediatric surgery, although side effects limit the use, such as illusions, delire and so on. KTM's antinociceptive effects is not only mediated by NMDA receptors, but also conducted by acetylcholine receptors, opioid receptors, substance P receptor as well as monoamines from descending inhibitory system. KTM does have obvious analgesic effect. But how does ketamine affect the presynaptic neurotransmitter release in the substansia gelatinosa of the spinal cord, which is an important action in spinal antinociception, is unknown. So this study aimed to investigate the effect of ketamine on presynaptic neurotransmitter release in SG of the spinal cord.The clinical effective concentration of KTM was used to investigate the effects of ketamine on presynaptic neurotransmitter release in substansia gelatinosa of the spinal cord. Under voltage clamp model and using the infrared visual whole cell patch clamp technique, we observed the effects of KTM on frequencies and amplitudes of the spontaneous inhibitory and excitatory postsynaptic currents (sIPSCs and sEPSCs). The results showed:①With the voltage clamped at 0 mV, 10-5 mol/L AP-V and 10-6 mol/L CNQX had been added to artificial cerebrospinal fluid (ACSF), and then the sIPSCs were recorded. After applying 10-4 mol/L KTM, the frequency of sIPSCs were 127.93%±25.17% (P<0.05), the amplitude were 104.78%±11.35% (P>0.05, n=7).②With the voltage clamp at -70 mV,after 3×10-7 mol/L strychnine and 10-6 mol/L bicuculline added to ACSF, the sEPSCs were observed. 10-4 mol/L KTM had effects on the frequency of sEPSCs at 97.89%±4.06%, while the amplitude at 101.63%±7.66% (P>0.05, n=8). The present results suggest:①KTM increases the frequency of sIPSCs, but dose not obviously influence the amplitude. The effect of KTM in SG might be mainly through the increase of inhibitory neurotransmitter release. That is, KTM triggers the increasing of presynaptic inhibitory neurotransmitter release in SG, where as does no obvious influence on postsynaptic neuron at all.②KTM had no noticeable effect on the frequency and amplitude of sEPSCs,in other words, KTM in the SG could not influence the excitatory neural signals transmission significantly. Such effects of KTM may be one of its mechanisms underlying the anesthetic and analgesic functions in the SG.
|
PDF Full Text Request