Kapsaisin Uygulamasının Diyafram Kas Kasılması Üzerindeki Akut Etkileri ve TRPV1 Reseptörünün Rolü

Öz

Epilepside Ani Beklenmeyen Ölüm (SUDEP), öncelikle nöbetlerin neden olduğu solunum yetmezliği ve solunumun tamamen durmasıyla ilişkilidir. Bu çalışmanın amacı, düşük doz pentilenetetrazol (PTZ) ile indüklenen absans epilepsili sıçanların diyafram kaslarında bazal kasılma dinamiklerini ve kalsiyum regülasyonunu araştırmak ve TRPV1 kalsiyum kanalının aktivatörü olan kapsaisinin, TRPV1, RyR1, hücresel kalsiyum kinetiği ve ex vivo mekanistik kasılma özellikleri üzerindeki doza bağımlı etkilerini incelemektir. Dört grup oluşturmak için otuz iki erkek sıçan (n=8/grup) kullanıldı: Kontrol, PTZ (25 mg/kg), PTZ + 1 μM kapsaisin ve PTZ + 10 μM kapsaisin. İzole diyafram kası şeritleri bir organ banyosuna yerleştirildi ve izometrik kasılma parametreleri 0,2 Hz'lik bazal frekansta ve 1-5 Hz'lik frekans aralığında kaydedildi. Kas dokularındaki TRPV1 ve RyR1 mRNA ekspresyon seviyeleri, kasılma kayıtlarının ardından qRT-PCR kullanılarak analiz edildi. Kontrol grubuyla karşılaştırıldığında, PTZ grubunda tüm stimülasyon frekanslarında kasılma ve gevşeme süreleri uzadı ve maksimum gevşeme hızı ile toplam kasılma kuvveti anlamlı derecede azaldı (p<0,05). PTZ grubunda RyR1 ekspresyonu moleküler düzeyde azaldı, TRPV1 ekspresyonu ise anlamlı derecede arttı (p<0,0001). Organ banyosuna düşük dozda 1 μM kapsaisin uygulanması, bozulan tüm mekanistik kasılma parametrelerini ve iyon kanalı gen ekspresyon seviyelerini normal kontrol seviyelerine geri getirdi. Yüksek doz kapsaisin kas fonksiyonunu inhibe ederken, düşük doz kapsaisin TRPV1 ve RyR1 arasındaki etkileşim yoluyla kalsiyum dengesini geri kazandırarak miyoprotektif bir etki gösterir.

Anahtar Kelimeler

• Absans Epilepsi
• Diyafram
• Kapsaisin
• TRPV1
• RyR1
• SUDEP

Acute Effects of Capsaicin Administration on Diaphragm Muscle Contraction and the Role of the TRPV1 Receptor

Öz

Sudden Unexpected Death in Epilepsy (SUDEP) is primarily associated with respiratory failure and complete cessation of respiration caused by seizures. The aims of this study were to investigate basal contraction dynamics and calcium regulation in diaphragmatic muscles of rats with absence epilepsy induced by low-dose pentylenetetrazol (PTZ), and to investigate the dose-dependent effects of capsaicin, an activator of the TRPV1 calcium channel, on TRPV1, RyR1, cellular calcium kinetics, and mechanistic contraction properties ex vivo. Thirty-two male rats (n=8/group) were used to form four groups: Control, PTZ (25 mg/kg), PTZ + 1 μM capsaicin, and PTZ + 10 μM capsaicin. Isolated diaphragmatic muscle strips were placed in an organ bath, and isometric contraction parameters were recorded at a basal frequency of 0.2 Hz and a frequency range of 1–5 Hz. TRPV1 and RyR1 mRNA expression levels in muscle tissues were analyzed using qRT-PCR following contraction recordings. Compared to the control group, the PTZ group showed prolonged contraction and relaxation times at all stimulation frequencies, and the maximum relaxation velocity and total contractile force were significantly reduced (p<0.05). RyR1 expression was downregulated at the molecular level in the PTZ group, while TRPV1 expression was significantly increased (p<0.0001). Application of a low dose of 1 μM capsaicin to the organ bath restored all disrupted mechanistic contraction parameters and ion channel gene expression levels to normal control levels. While high-dose capsaicin inhibits muscle function, low-dose capsaicin exerts a myoprotective effect by restoring calcium balance through the interaction between TRPV1 and RyR1.

Anahtar Kelimeler

• Absence Epilepsy
• Diaphragm
• Capsaicin
• TRPV1
• RyR1
• SUDEP

Kaynakça

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