Desmedt L, Simaels J, Van Driessche W
Laboratory for Physiology, KULeuven, Belgium.
J Gen Physiol. 1993 Jan;101(1):103-16. doi: 10.1085/jgp.101.1.103.
We examined the effect of the local anesthetic tetracaine on the Ca(2+)-blockable, poorly selective cation channels in the isolated skin of Rana temporaria and the urinary bladder of Bufo marinus using noise analysis and microelectrode impalements. Experiments with frog skin demonstrated that mucosal concentrations of the compound up to 100 microM did not affect the Na+ current through type S channels (slowly fluctuating, UO2(2+)-blockable channels) and the associated noise. On the other hand, 20 microM mucosal tetracaine already suffices to inhibit approximately 50% of the current carried by Cs+ and Na+ through channel type F (fast fluctuating, UO2(2+)-insensitive channel) and So of the associated Lorentzian component. With 100 microM of the inhibitor the current and So values were reduced by at least 70-80%. The time course of the response to serosal tetracaine was markedly slower and the effects on the current and So were smaller. Possible effects on the basolateral K+ conductance were excluded on the basis of the lack of response of transepithelial K+ movements to 100 microM tetracaine. UO2(2+) and tetracaine together blocked the poorly selective cation pathways almost completely. Moreover, both agents retain their inhibitory effect in the presence of the other. In toad urinary bladder, the Ca(2+)-blockable channel is also tetracaine blockable. The concentration required for half-maximal inhibition is approximately 100 microM in SO4(2-) and approximately 20 microM in Cl-. The data with tetracaine complement those obtained with UO2(2+) and support the idea that the Ca(2+)-blockable current proceeds through two distinct classes of cation channels. Using tetracaine and UO2(2+) as channel-specific compounds, we demonstrated with microelectrode measurements that both channel types are located in the granulosum cells.
我们使用噪声分析和微电极穿刺技术，研究了局部麻醉药丁卡因对林蛙离体皮肤和海蟾蜍膀胱中可被Ca(2+)阻断的、选择性较差的阳离子通道的影响。对蛙皮的实验表明，该化合物黏膜浓度高达100微摩尔时，不会影响通过S型通道（缓慢波动、可被UO2(2+)阻断的通道）的Na+电流及相关噪声。另一方面，20微摩尔的黏膜丁卡因已足以抑制约50%由Cs+和Na+通过F型通道（快速波动、对UO2(2+)不敏感的通道）所携带的电流以及相关洛伦兹分量的So。使用100微摩尔的抑制剂时，电流和So值至少降低70 - 80%。对浆膜丁卡因反应的时间进程明显较慢，对电流和So的影响较小。基于上皮钾离子运动对100微摩尔丁卡因无反应，排除了对基底外侧钾离子电导可能的影响。UO2(2+)和丁卡因共同作用几乎完全阻断了选择性较差的阳离子通道。此外，两种药物在彼此存在的情况下仍保持其抑制作用。在蟾蜍膀胱中，可被Ca(2+)阻断的通道也可被丁卡因阻断。在SO4(2-)中半最大抑制所需浓度约为100微摩尔，在Cl-中约为20微摩尔。丁卡因的数据补充了用UO2(2+)获得的数据，并支持可被Ca(2+)阻断的电流通过两类不同阳离子通道的观点。使用丁卡因和UO2(2+)作为通道特异性化合物，我们通过微电极测量证明这两种通道类型都位于颗粒层细胞中。
