Mechanical transduction by ion channels:A cautionary tale

• 作者: Frederick Sachs
• 来源期刊: 世界神经病学杂志
• 学科: 医学
• 关键词: Channel MECHANICAL Patch Force Tension BILAYER Domain OSMOTIC TRANSDUCTION BIOMECHANICS
• 年，卷（期）: 2015,（3）
• 页码范围: 74-87
• 页数: 14页
• 分类号: R

摘要

Mechanical transduction by ion channels occurs in all cells.The physiological functions of these channels have just begun to be elaborated,but if we focus on the upper animal kingdom,these channels serve the common sensory services such as hearing and touch,provide the central nervous system with information on the force and position of muscles and joints,and they provide the autonomic system with information about the filling of hollow organs such as blood vessels.However,all cells of the body have mechanosensitive channels(MSCs),including red cells.Most of these channels are cation selective and are activated by bilayer tension.There are also K+selective MSCs found commonly in neurons where they may be responsible for both general anesthesia and knockout punches in the boxing ring by hyperpolarizing neurons to reduce excitability.The cationic MSCs are typically inactive under normal mechanical stress,but open under pathologic stress.The channels are normally inactive because they are shielded from stress by the cytoskeleton.The cationic MSCs are specifically blocked by the externally applied peptide GsMtx4(aka,AT-300).This is the first drug of its class and provides a new approach to many pathologies since it is nontoxic,non-immunogenic,stable in a biological environment and has a long pharmacokinetic lifetime.Pathologies involving excessive stress are common.They produce cardiac arrhythmias,contraction in stretched dystrophic muscle,xerocytotic and sickled red cells,etc.The channels seem to function primarily as“fire alarms”,providing feedback to the cytoskeleton that a region of the bilayer is under excessive tension and needs reinforcing.The eukaryotic forms of MSCs have only been cloned in recent years and few people have experience working with them.“Newbies”need to become aware of the technology,potential artifacts,and the fundamentals of mechanics.The most difficult problem in studying MSCs is that the actual stimulus,the force applied to the channel,is not known.We don’t have direct access to