Jacobson David, Herson Paco S, Neelands Torben R, Maylie James, Adelman John P
Department of Molecular and Medical Genetics, Oregon Health and Sciences University, Portland, Oregon, USA.
Muscle Nerve. 2002 Dec;26(6):817-22. doi: 10.1002/mus.10280.
Skeletal muscle hyperexcitability is characteristically associated with denervation. Expression of SK3, a small conductance Ca(2+)-activated K(+) channel (SK channel) in skeletal muscle is induced by denervation, and direct application of apamin, a peptide blocker of SK channels, dramatically reduces hyperexcitability. To investigate the role of SK3 channels in denervation- induced hyperexcitability, SK3 expression was manipulated using a transgenic mouse that harbors a tetracycline-regulated SK3 gene. Electromyographic (EMG) recordings from anterior tibial (AT) muscle showed that denervated muscle from transgenic or wild-type animals had equivalent hyperexcitability that was blocked by apamin. In contrast, denervated skeletal muscle from SK3tTA mice lacking SK3 channels showed little or no hyperexcitability, similar to results from wild-type innervated skeletal muscle. However, innervated skeletal muscle from SK3tTA mice containing SK3 channels did not show hyperexcitability. The results demonstrate that SK3 channels are necessary but not sufficient for denervation-induced skeletal muscle hyperexcitability.
骨骼肌兴奋性过高通常与去神经支配有关。小电导钙激活钾通道（SK通道）之一的SK3在骨骼肌中的表达是由去神经支配诱导的，直接应用蜂毒明肽（一种SK通道的肽类阻滞剂）可显著降低兴奋性过高。为了研究SK3通道在去神经支配诱导的兴奋性过高中的作用，利用携带四环素调控SK3基因的转基因小鼠来调控SK3的表达。来自胫前肌的肌电图（EMG）记录显示，转基因或野生型动物的去神经支配肌肉具有同等的兴奋性过高，且被蜂毒明肽所阻断。相比之下，缺乏SK3通道的SK3tTA小鼠的去神经支配骨骼肌几乎没有或没有兴奋性过高，类似于野生型有神经支配的骨骼肌的结果。然而，含有SK3通道的SK3tTA小鼠的有神经支配骨骼肌并未表现出兴奋性过高。结果表明，SK3通道对于去神经支配诱导的骨骼肌兴奋性过高是必要的，但不是充分的。
