骨格筋の筋収縮メカニズム
①中枢からの骨格筋収縮の指令は活動電位により電気的信号として運動神経線維を伝わってきて運動神経終末までやってくる。運動神経線維は自律神経のように中枢から支配器の間で神経節でニューロン交代(乗り換え)をすることがないので、節前線維と節後線維という区別がなく1本である。
②活動電位が伝わるとシナプス前膜が脱分極して電位依存性カルシウムイオンチャネルが開く。
③カルシウムイオンが運動神経終末に流入してきて運動神経細胞内のカルシウムイオン濃度が上がると、シナプス小胞がシナプス前膜と膜融合してアセチルコリンをシナプス間隙に開口分泌(exocytosis)する。ここで活動電位という電気的信号がアセチルコリンという化学的信号に変わることになる。
④放出されたアセチルコリンは運動終板上にあるニコチン性アセチルコリン受容体(Nm受容体)に結合する。
⑤ニコチン性アセチルコリン受容体(Nm受容体)にアセチルコリンが結合するとナトリウムイオンが流入して運動終板が脱分極する。ここでアセチルコリンという化学的信号は再び活動電位という電気的信号に戻る。
⑥このようにして発生した活動電位は横行小管(T管)上にあるジヒドロピリジン受容体:DHPR(電位依存性カルシウムチャネル:Cav1.1=L型1)に伝わる。
⑦活動電位が伝わるとジヒドロピリジン受容体は構造が変化する。
⑧ジヒドロピリジン受容体の構造が変化すると筋小胞体上にあるカルシウムチャネルであるリアノジン受容体Ⅰ型が活性化されてカルシウムイオンが筋小胞体から放出されることになる。
⑨放出されたカルシウムイオンがトロポニンに結合するとトロポミオシンがアクチンから引き離されて、ミオシン頭部がアクチンと結合できるようになる。こうしてアクチンとミオシンは相互作用(滑走)ができるようになり筋収縮が起こる。
心筋の筋収縮メカニズム
心臓拍動の自動中枢である洞房結節が1回活動電位が発生させると心臓は1回拍動する。
つまり、心筋の収縮は洞房結節が発生させた活動電位が刺激伝導系を通じて伝播していく結果として起こっているのである。
通常、心筋細胞は隣接した細胞に活動電位が発生しない限りは静止膜電位を保ち脱分極することはない。
しかし、洞房結節細胞(房室接合部周辺やHis束の心筋細胞も洞房結節細胞ほどではないが自動能を持つ)は外部からの刺激が無くても内因性に活動電位を発生させて自動的に興奮する自動能を持つ。
また、刺激伝導系の心筋細胞も自動能を持つものの通常は洞房結節細胞に追従する形となっている。刺激伝導系上位の細胞から十分な電位が伝わらない場合は、下位の細胞が自動能を発揮して補充する。
骨格筋が運動神経の指令によって筋収縮を起こしている機構とは異なることに注意する必要がある。
心筋と骨格筋の筋収縮メカニズムの違い
活動電位発生機構の違い
心筋は不随意筋であるのに対して、骨格筋は随意筋である。このため、骨格筋細胞が運動神経の指令によって脱分極を生じて筋収縮を起こしている機構と心筋が収縮する機構は異なる。
心筋細胞は隣接した心筋細胞の活動電位が伝播した結果として脱分極を生じる。
洞房結節細胞が自動能を持っており、刺激伝導系を通じて心臓全体に活動電位を行き渡らせるペースメーカーとして機能している。
また、心筋細胞に活動電位が発生した結果として起こる心筋収縮までの機構も骨格筋細胞のものとは異なる。
活動電位の信号を細胞内に伝える機構の違い
心筋ではジヒドロピリジン受容体:DHPR(電位依存性カルシウムチャネル:Cav1.2=L型2)からのカルシウムイオン流入がカルシウムイオン依存的にリアノジン受容体Ⅱ型を活性化する。これは構造変化のみでリアノジン受容体Ⅰ型を活性化させる骨格筋にあるジヒドロピリジン受容体:DHPR(電位依存性カルシウムチャネル:Cav1.1=L型1)とは作用の仕方が異なる。
つまり、心筋の収縮の際に筋小胞体からカルシウムイオンが放出されるためにはリアノジン受容体Ⅱ型を活性化するためにカルシウムイオンのジヒドロピリジン受容体:DHPR(電位依存性カルシウムチャネル:Cav1.2=L型2)を通した心筋細胞内流入が必要であり、この筋小胞体からのカルシウムイオン放出様式をカルシウムイオン誘発性カルシウムイオン放出という。
一方で、骨格筋の収縮の際は筋小胞体からカルシウムイオンが放出されるためにカルシウムイオンの骨格筋細胞内流入が必要がなく、このカルシウムイオン放出様式を脱分極誘発性カルシウムイオン放出という。ジヒドロピリジン受容体とリアノジン受容体には種類があり、筋収縮に関わる方法がそれぞれ異なるということである。
滑り説
滑り説で説明できるのは横紋筋(骨格筋・心筋)の筋収縮である。平滑筋はまた別の機構で筋収縮が起こるとされている。
筋弛緩時
トロポニンがアクチンに結合して、トロポミオシンはミオシン頭部がアクチンと結合できないように働いている。
このためアクチンとミオシンは相互作用(滑走)ができず筋収縮は起こらない。
筋収縮時
カルシウムイオンがトロポニンに結合するとトロポミオシンの構造が変化してミオシン頭部がアクチンと結合できるようになる。
こうしてアクチンとミオシンは相互作用(滑走)ができるようになり筋収縮が起こる。
血管平滑筋収縮・弛緩のメカニズム
平滑筋の筋収縮は滑り説では説明できない
滑り説で説明できるのは横紋筋(骨格筋・心筋)の筋収縮である。
平滑筋には横行小管が存在しない。また、トロポニンも存在しない。
このため、平滑筋の筋収縮は滑り説では説明することができない。
平滑筋の筋収縮・筋弛緩の鍵を握っているのは「ミオシン頭部ATP分解酵素の活性化・不活性化」である。
平滑筋を筋収縮させる機構はミオシン頭部ATP分解酵素を活性化させるためにミオシン軽鎖キナーゼ(ミオシン軽鎖リン酸化酵素)を活性化させてミオシン軽鎖ホスファターゼ(ミオシン軽鎖脱リン酸化酵素)を抑制するように働き、平滑筋を筋弛緩させる機構はミオシン頭部ATP分解酵素を不活性化させるためにミオシン軽鎖キナーゼを抑制してミオシン軽鎖ホスファターゼを活性化させるように働く。
骨格筋や心筋ではミオシン頭部のATP分解酵素(ATPase)が常に活性型になっているので、平滑筋のようにミオシン軽鎖キナーゼがATP分解酵素(ATPase)を活性化する必要がない。
平滑筋の筋収縮メカニズム
①機械的な刺激や脱分極によって電位依存性カルシウムイオンチャネルが開いて細胞外から細胞内にカルシウムイオンが流れ込む。また、自律神経が受容体作動性カルシウムイオンチャネルを開いて細胞外から細胞内にカルシウムイオンを流し込んだり、Gqタンパク質共役受容体を通じてIP3誘発性カルシウムイオン遊離を引き起こす。
②平滑筋細胞内でカルシウムイオン濃度が高まるとカルシウムイオンはカルシウムイオン結合タンパク質であるカルモジュリンと結合する。
③カルシウムイオンと結合したカルモジュリンはミオシン軽鎖キナーゼ(ミオシン軽鎖リン酸化酵素)を活性化する。
④また、Gqタンパク質共役受容体を通じて活性化されたプロテインキナーゼCはミオシン軽鎖ホスファターゼ(ミオシン軽鎖脱リン酸化酵素)を抑制することで筋収縮を促進する。
平滑筋の筋弛緩メカニズム
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Hydroquinone: Uses, Side Effects, Risks, And More
What Is Hydroquinone and What Are Its Uses?
Hydroquinone, also known as 1,4-dihydroxybenzene, is a natural skin lightener derived
from aromatic plants like bearberry or green tea. It is commonly
used to reduce pigmentation and improve skin texture.
Hydroquinone works by inhibiting the production of melanin, the pigment responsible for dark spots
and uneven skin tones. While it has been used for centuries
in traditional medicine, its application must be done carefully due
to potential side effects.
How Hydroquinone Works
Hydroquinone works by blocking the enzyme tyrosinase, which is responsible for melanin production. By inhibiting
this enzyme, it helps fade hyperpigmentation and reduces dark spots over time.
Its effectiveness is often compared to other skin lighteners, with results usually visible within a few months of consistent use.
Skin Conditions That Benefit From Its Use
Hydroquinone is particularly effective for treating several skin conditions:
Melasma: A condition characterized by dark patches on the face,
often caused by hormonal changes. Hydroquinone helps
reduce pigmentation and lighten these areas.
Eczema: While not a cure, hydroquinone can help alleviate the redness and inflammation associated
with eczema when applied to affected areas.
Acne Scars: By inhibiting melanin production, hydroquinone can help fade
the dark scars left by acne.
Psoriasis: Hydroquinone may help reduce the appearance
of psoriatic scales and patches when used as part of
a broader treatment plan.
Age Spots: One of the most common uses, hydroquinone effectively lightens age-related hyperpigmentation on the face and hands.
Getting an Expert Opinion
Before using hydroquinone, it is crucial to consult with
a dermatologist. They can assess your skin condition, determine if hydroquinone is appropriate for you, and provide guidance on safe application methods.
Is a Skin-Lightening Cream Safe for All Skin Types?
While hydroquinone is generally considered safe when used as directed, it can cause irritation or burns in some individuals.
Those with sensitive skin, rosacea, or eczema may want to avoid using hydroquinone-based products.
How to Use It
Apply hydroquinone cream as recommended by your dermatologist,
typically once daily in the morning and evening.
Always follow the dosage instructions on the product label and avoid applying it in excess or without guidance
from a healthcare professional.
What Happens When You Stop
If you discontinue using hydroquinone, you may notice a
recurrence of dark spots as melanin production resumes.
Consistent use is key to maintaining results, so consider
long-term strategies for skin health with your doctor’s advice.
Potential Risks and Side Effects
Common side effects include mild irritation or burns, especially in sensitive areas like the face.
Overuse can lead to peeling or dryness, so it is important to adhere to recommended
application frequencies. Long-term use should be
discussed with a dermatologist to assess potential health risks.
Natural Alternatives to Hydroquinone
If you are considering alternatives, natural options like antioxidants (Vitamins A and
C) and plant-based acids can offer similar benefits without the risks associated with hydroquinone.
These ingredients work synergistically to reduce pigmentation and promote skin health.
Antioxidants Such as Vitamins A and C
Vitamin C is particularly effective at brightening skin tone
and protecting against oxidative stress, while Vitamin B3 (niacinamide) helps reduce melanin production and
improves skin elasticity. Together, these antioxidants can provide natural alternatives to hydroquinone.
Plant-Based Acids
Plant-based acids like bearberry extract contain hydroquinone,
which can help lighten skin pigmentation naturally.
However, excessive use may lead to irritation, so moderation is key when using these
products.
Vitamin B3
Vitamin B3 (niacinamide) is another natural alternative
that helps reduce hyperpigmentation and improve skin texture.
It works by inhibiting melanin transfer in the skin, leading to a brighter complexion over time.
Summary
Hydroquinone is an effective treatment for certain skin conditions, but its use must be approached with caution due to
potential side effects and risks. Consulting with a dermatologist is essential
before starting any new skincare regimen. Natural
alternatives like antioxidants and plant-based
acids can offer similar benefits without the associated health risks.
A Word From Verywell
“Hydroquinone can be an effective treatment for certain skin conditions, but it should only be used under medical supervision,”
says Dr. Jane Kim, a dermatologist at Verywell.
“The potential for irritation and long-term health effects necessitates careful consideration and professional guidance.”
Frequently Asked Questions
Q: Is hydroquinone safe for all skin types?
A: Not necessarily. It may cause irritation in individuals with sensitive skin conditions like rosacea or eczema.
Q: How long does it take to see results from hydroquinone?
A: Results typically appear within a few months of consistent use, but this
can vary depending on the individual and the severity of their condition.
Q: Are there natural alternatives to hydroquinone?
A: Yes, antioxidants like Vitamins A and C, as well as plant-based acids,
can provide similar benefits without the associated risks of hydroquinone.
Q: Can hydroquinone be used on the face?
A: While it is effective for facial conditions like melasma, it should only be used under
medical supervision to avoid irritation or burns.
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