Regulation of Ketamine and NMDA Responses by Intracellular and Exteranl pH Changes in Locus Coeruleus Neurons

• Main Authors: Mei-Hui Sun, 孫美慧
• Other Authors: Tsai-Hsien Chiu
• Format: Others
• Language: zh-TW
• Published: 2000
• Online Access: http://ndltd.ncl.edu.tw/handle/22638315381965065257

碩士 === 國立陽明大學 === 生理學研究所 === 88 === It has been commonly assumed that both extracellular pH ( pH0 ) and intracellular pH ( pHi ) in various excitable cells and tissues are well regulated by homeostatic mechanisms. Changes in pH0 and pHi tend to exert profound effects on the properties of cells, because enzymes and ion channels are clearly affected by changes in pH . The clinically relevant observations that changes in acid-base balance caused by general anesthetics during anesthesia and surgery occur very often. Ketamine, a well characterized non-competitive NMDA receptor antagonist, has been used clinically as an analgesic and anaesthetic for the last 30 years. Furthermore, the activation of NMDA receptors in neurons from many areas of the CNS is inhibited by protons , within the physiological range of extracellular pH . In the present study, we have examined the regulation of ketamine’s actions on NMDA receptors by intracellular and external pH changes in locus coeruleus ( LC ) by intracellular recording. The increasing firing rate and depolarization of LC neurons produced by superfusion of 10M NMDA was decreased by 91.7 % and 89.0 % when pre- superfusion of 100 M ketamine. The inhibition of firing rate by ketamine was decreased 35.5 % in extracellular acidic aCSF ( pH 6.81 ). The inhibition of depolarization by ketamine was decreased 29 % in external basic aCSF ( pH 8.1 ). Intracellular pH change did not influence the actions of ketamine while superfusion of NMDA . These results suggest that ketamine’s actions on NMDA receptors were modulated by protons in the LC neurons. Extracellular acidification ( pH 6.81 ) and alkalinization ( pH 8.1 ) suppressed the ability of ketamine to inhibit the NMDA-caused firing rate raise and depolarization in LC neurons. The modulation of ketamine by protons may play a role in the clinical application.