Stretch-activated or stretch-gated ion channels are ion channels - 근육을 압박하거나 스트레칭하면 ???

[문형철]

인장활성이온채널

근방추의 늘어남으로 인해서 이온채널이 열려 활성화되는 과정

근육통이 발생했을때, 허혈성 압박, 롤핑, 근막이완, 치료적 마사지, 진동건, 충격파 등으로 자극을 주면 통증이 줄어드는 이유

근육은 진동, 압박, 스트레치, 촉각, 열 등의 물리적 자극에 의해 이온채널이 열리면서 근육긴장이 해소된다. 모두 근방추의 스트레치 반사기전에 의한다. ????

Stretch-activated or stretch-gated ion channels are ion channels which open their pores in response to mechanical deformation of a neuron's plasma membrane. Opening of the ion channels depolarizes the afferent neuron producing an action potential with sufficient depolarization.^[1] 

- 스트레치-활성화 또는 스트레치-문 이온채널은 그들의 pore가 신경의 plasma membrane의 기계적 변형자극에 반응하여 열리는 이온채널임. 

- 이온채널의 열림은 충분한 탈분극과 함께 활동전위를 생성하는 구심성 신경 탈분극을 일으킴. 

Channels open in response to two different mechanisms: the prokaryotic model and the mammalian hair cell model.^[2][3] Stretch-activated ion channels have been shown to detect vibration, pressure, stretch, touch, sounds, tastes, smell, heat, volume, and vision.^[4][5][6] 

- 스트레치-활성화 이온채널은 진동, 압박, 스트레칭, 터치, 소리, 맛, 냄새, 열, 시각등에서 발견됨. 

Stretch-activated ion channels have been categorized into three distinct "superfamilies": the ENaC/DEG family, the TRP family, and the K1 selective family. These channels are involved with bodily functions such as blood pressure regulation.^[7] They are shown to be associated with many cardiovascular diseases.^[3] 

Stretch-activated channels were first observed in chick skeletal muscles by Falguni Guharay and Frederick Sachs in 1983 and the results were published in 1984.^[8] Since then stretch-activated channels have been found in cells from bacteria to humans as well as plants.

인장활성이온채널의 개념

Stretch-activated ion channels are mechanotransducers which conduct ionic currents by responding to stress in the cell membrane. To be identified as stretch-activated, the ion channel must open and close in response to membrane tension.^[7]

인장활성이온채널은  mechanotransducers임. 이것은 세포막에서 스트레스압박에 반응하여 이온이 흐르는 것을 말함. 

인장활성을 증명하기 위해서 이온채널은 막 긴장에 반응하여 열리고 닫혀야 함. 

Mechanotransduction, an electrical signal resulting from a mechanical stimulus, occurs via the opening of stretch-activated ion channels due to membrane deformation. The opening of these channels results in a non-specific ionic flow, which depolarizes the afferent nerve fiber, and may produce action potentials with sufficient depolarization.^[1] The opening of these channels is central to a neuron’s response to pressure, often osmotic pressure and blood pressure, to regulate ionic flow in internal environments.^[2] 

압력전도,  기계적 자극으로부터 오는 전기적 자극은 막변형으로 이온채널이 스트레치로 활성화되어 열림. 

이 채널 열림으로 비특이적 이온 흐름을 야기함. 구심신경섬유가 탈분극되어 활동전위를 일으킬 수 있음. 

압력(삼투압, 혈압)에 반응하여 이 채널의 열림은 

참고) mechanotransduction

mechanotransduction in repair and regeneration.pdf

Intracellular mechanisms of mechanotransduction. 

Mechanical force is sensed by the integumentary system and activates multiple intracellular signaling pathways. Several membrane-bound mechanosensory complexes have been described and include stretch-activated ion channels, growth factor receptors, integrins, and G-protein-coupled receptors. 

Of primary significance in fibroblasts and keratinocytes is matrix–integrin activation of focal adhesion complexes that contain focal adhesion kinase (FAK). Mechanical force is transmitted across the cell membrane to activate downstream biochemical pathways including but not limited to calcium-dependent targets, nitric oxide (NO) signaling, mitogen-associated protein kinases (MAPKs), Rho GTPases, and phosphoinositol-3-kinase (PI3K). The convergence of these signals results in the activation of transcription factors that translocate to the nucleus and activate mechanoresponsive genes (adapted from Jaalouk and Lammerding, 2009).

There are two mechanisms for which these channels open.  The prokaryotic model suggests that stretch-activated channels open directly in response to force to the membrane, whereas the mammalian hair cell model involves a tether bound both to the channel and to the extracellular matrix or cytoskeleton. Force on the membrane then displaces the tether, creating tension which opens the channel.^[2]

인장활성이온채널의 기능

Stretch-activated ion channels are of use in the initial formation of an action potential from a mechanical stimulus, for example by the mechanoreceptors in an animal's vibrissae (whiskers).

Afferent nerve fibers responsible for sensory stimulus detection and feedback are especially sensitive to stimulation. This results from the specialized mechanoreceptor cells that are superimposed upon the afferent nerve fibers. Stretch-activated ion channels are located on these mechanoreceptor cells and serve to lower the action potential threshold, thus making the afferent nerves more sensitive to stimulation. Afferent nerve endings without mechanoreceptor cells are called free nerve endings. They are less sensitive than the encapsulated afferent fibers and generally function in the perception of pain.^[1]

Stretch-activated ion channels are responsible for many bodily functions in mammals. In the skin they are responsible for sensing vibration, pressure sensation, stretch, touch, and light touch.^[4][5] They are expressed in sensory modalities including taste, hearing, smell, heat sensation, volume control, and vision.^[2][3][6] They can also regulate internal functions of our body including, but not limited to, osmotic pressure in cells, blood pressure in veins and arteries, micturition, and heart contractility.^[2][6] 

In addition to these functionalities, stretch-activated ion channels have also been found to be involved with balance and proprioceptive sensation.^[2]

인장활성이온채널의 사례

The different families of stretch-activated ion channels are responsible for different functions around the body. The DEG/ENaC family consists of two subgroups: the ENaC subfamily regulates Na+ reabsorption in kidney and lung epithelia; the ASIC subfamily is involved in fear conditioning, memory formation, and pain sensation.^[9] The TRP superfamily of channels are found in sensory receptor cells that are involved in heat sensation, taste, smell, touch, and osmotic and volume regulation.^[3] MscM, MscS, and MscL channels (mechanosensitive channels of mini, small, and large conductance) regulate osmotic pressure in cells by releasing intracellular fluid when they become too stretched.^[2] In the body, a possible role in myoblast development has been described.^[10] Furthermore, mechanically gated ion channels are also found in the stereocilia of the inner ear. Sound waves are able to bend the stereocilia and open up ion channels leading to the creation of nerve impulses.^[11] These channels also play a role in sensing vibration and pressure via activation of Pacinian corpuscles in the skin.^[12]

조절

Stretch-activated ion channels are one of the three main types of ionotropic receptors, or channel-linked receptors. These channels open when mechanical forces of stretch or pressure is applied to the channels, causing them to undergo a conformational change. This change allows ions to pass through.^[13] The channels may also be pulled open due to tension on the membrane itself.^[13] Opening the channels allows ions to which they are permeable to flow down their electrochemical gradients into or out of the cell, causing a change in membrane potential.

All types of stretch-activated ion channels respond to mechanical stimuli with a similar mechanism. A stimulus resulting from a deformation of the capsule on the afferent neuron causes a stretch in the membrane. This mechanical deformation causes stretch-sensitive channels to have an increased probability of opening. A depolarization of the afferent nerve fiber occurs as the stretch-activated cation channel opens. An action potential fires if the cell is depolarized above threshold and it propagates to the CNS.^[1] The sensory stimuli that excite stretch-activated channels are regulated by Ab and Aa nerve fibers. 

These fibers have low thresholds and originate from mechanosensory neurons in the dorsal root ganglion.^[4] ). Channels that have traditionally been known as just “voltage-“ or “ligand-gated” have also been found to be mechanically sensitive as well. Channels exhibit mechanical sensitivity as a general property. However, mechanical stress affects various types of channels in different ways. Voltage and ligand gated channels can be modified slightly by mechanical stimulation, which might change their responsiveness or permeability slightly, but they still respond primarily to voltage or ligands, respectively.^[7]

조절기전

There are two different types of stretch-activated channels between which it is important to distinguish: mechanically-gated channels, which are directly influenced by mechanical deformations of the membrane, and mechanically-sensitive channels, which are opened by second messengers released from the true mechanically-gated channel.^[4]

Two different mechanisms have been found to open stretch-activated ion channels: Mechanical deformations in the cell membrane can increase the probability of the channels opening. Proteins of the extracellular matrix and cytoskeleton are tethered to extra - and intra-cytoplasmic domains, respectively, of the stretch-activated ion channels. 

Tension on these mechanosensory proteins causes these proteins to act as a signaling intermediate, resulting in the opening of the ion channel.^[4] All known stretch-activated ion channels in prokaryotic cells have been found to be opened by direct deformation of the lipid bilayer membrane.^[2] Channels that have been shown to exclusively use this mechanism of gating are the TREK-1 and TRAAK channels. In studies using mammalian hair cells, the mechanism that pulls on proteins tethered from the intra- and extra-cytoplasmic domain of the channel to the cytoskeleton and extracellular matrix, respectively, is the most likely model for ion channel opening.^[2]

[박건용]

-허혈성압박,롤핑,근막이완,치료적마사지,진동건,충격파 등으로 자극을 주면 통증이 줄어드는 이유: 근육은 진동, 압박, 스트레치, 촉각, 열 등의 물리적 자극에 의해 이온채널이 열리면서 근육긴장이 해소된다. 모두 근방추의 스트레치 반사기전에 의함.
-인장활성이온채널은 mechanotransducers임. 세포막에서 스트레스압박에 반응하여 이온이 흐르는 것을 말함
?? 인장활성이온채널은 neuron의 세포막에 있는 이온통로입니다. sounds, tastes, smell, vision보다 운동치료관점에서 vibration, pressure, stretch, touch 등의 기계적자극이 중요한데 이 자극을 받는 neuron은 근방추체, GTO, 인대,관절의 mechanoreceptor로 생각하면 될까요?

[이영호]

1. 근육통이 발생했을때 물리적 자극( 허혈성 압박, 롤핑, 근막이완, 치료적 마사지, 진동건, 충격파 등) 을 주면 통증이 줄어드는 이유 : 근육은 진동, 압박, 촉각, 열 등의 물리적 자극에 의해 이온채널이 열리면서 근육긴장이 해소. 근방추의 스트레치 반사기전에 의함.
2. mechanotransducers - 세포막에서 스트레스압박에 반응하여 이온이 흐르는 것임.
3. 쭉 읽다 보니 깊고 어려워서 여기까지만 이해하고 넘어갑니다.

[박수홍]

물리적 자극에 의해 이온채널이 열리면서 근육긴장이 해소 읽기