Electrical activity and cytosolic calcium regulate levels of tetrodotoxin-sensitive sodium channels in cultured rat muscle cells.
Electrical activity and cytosolic calcium regulate levels of tetrodotoxin-sensitive sodium channels in cultured rat muscle cells.
复制标题
电活动和胞质钙调节培养的大鼠肌肉细胞中河豚毒素敏感的钠通道的水平。
DOI：
10.1073/pnas.81.1.262
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发表时间：
1984
影响因子：
11.1
通讯作者：
Catterall,WA
中科院分区：
文献类型：
--
作者：
Sherman,SJ;Catterall,WA
通过对[3H]蛤蚌毒素的特异性结合，发现在布比卡因、河河蟹毒素或氯化钾中生长，对大鼠肌管原代培养中存在的自发电活动进行药物阻断，可使电压敏感的Na+通道数量增加38-83%。布比卡因对自发电活动的抑制和通道密度的增加表现出相同的剂量效应，在3.0微米时具有半最大效应。在1微米A23187（一种Ca2+特异性离子载体）的存在下，肌管的生长导致河豚毒素敏感通道的数量减少30-60%，但对[3H]蛤蚌毒素的亲和力没有变化。A23187能够克服布比卡因产生的通道密度增加。这些结果表明存在Ca2+介导的负反馈系统，其中电兴奋性可能通过改变河豚毒素敏感的Na+通道的数量来调节。
Pharmacological blockade of the spontaneous electrical activity present in primary cultures of rat myotubes by growth in bupivacaine, tetrodotoxin, or KCl was found to increase the number of voltage-sensitive Na+ channels 38-83% as measured by the specific binding of [3H]saxitoxin. The inhibition of spontaneous electrical activity and increase in channel density by bupivacaine displayed an identical dose response, with a half-maximal effect at 3.0 microM. Growth of myotubes in the presence of 1 microM A23187, a Ca2+-specific ionophore, resulted in a 30-60% decrease in the number of tetrodotoxin-sensitive channels with no change in affinity for [3H]saxitoxin. A23187 was able to overcome the increase in channel density produced by bupivacaine. These results suggest the presence of a Ca2+-mediated negative feedback system in which electrical excitability may be regulated by altering the number of tetrodotoxin-sensitive Na+ channels.