Ventral ve Dorsal Kök Aksonları Üzerine 4-Aminopiridinin Farklı Etkileri

Öz

Amaç: Motor ve Duysal sinir lifleri bir potasyum kanal blokörü olan 4-Aminopiridine karşı (4-AP) farklı yanıt verebilirler. Bu çalışmadaki amacımız sıçan ventral ve dorsal arka kök aksonlarının elektrofizyolojik özelliklerini 4-AP ve Birleşik Sinir Aksiyon Potansiyelleri (BSAP) aracılığı ile araştırmaktır.
Materyal-Metod: Wistar türü erkek sıçanlar ether anestezisi altında karotoid arter kesisi ile hızlı bir şekilde sakrifiye edildi. Lumbar (L-4) ventral ve dorsal kök aksonları laminektomi yöntemi ile hızlıca çıkarılıp 95% 02+5% CO2 ile gazlandırılan soğuk Krebs içine alındı. 4-AP etkisini değerlendirmek için BSAP kayıtları modifiye sukroz-gap aparatı ile in vitro olarak ölçüldü. Tüm deneyler 20-22 oC yürütüldü.
Bulgular: Ventral köklerden kayıtlanan BSAP toplam süresi 4-AP uygulaması ile uzadı ve dinlenim değerine dönmesi gecikti. Dorsal köklerde ise toplam BSAP süresi ventral köklere göre en az iki kat daha fazla uzadı. Ayrıca dorsal köklerde 4-AP sonrası dinlenim değerine dönerken belirgin bir hump (hörgüç) gözlendi. Bu fenomen ventral köklerde görülmedi. Ventral ve dorsal köklerden kayıtlanan BSAP latansları sırasıyla 256 ± 24 ve 508 ± 69 μs, iletim hızı ise 20,4 ± 2,4 ve 10,8 ± 1,4 m/s olarak ölçüldü.
Sonuç: Bu çalışmada sıçan motor ve duysal aksonları üzerine 4-AP’nin çok farklı etkilere sahip olduğunu gösterdik. Motor ve duysal sinir lifleri üzerine 4-AP’nin farklı etkileri, bu sinirlerde bulunan miyelinli-myelinsiz akson oranlarının ve akson çaplarının farklı olmalarından kaynaklanabilir. İlave olarak ventral ve dorsal kök aksonlarında nod veya paranodda bulunan potasyum-sodyum kanal farklılığından kaynaklanabilir.

Anahtar Kelimeler

• Ventral-Dorsal Kök
• Aksiyon Potansiyeli
• 4-Aminopiridin
• Sukrozgap

The Different Effects of 4-Aminophyridine on Ventral and Dorsal Root Axons

Öz

Aim: Rat motor and sensory nerve fibers may responses differently to the potassium channelblocking agent, 4-aminopyridine (4-AP). In this study we examined the electrophysiological properties of rat ventral and dorsal root axons with 4-AP and compound action potentials (CAP’s). Materials-Methods: Male Wistar rats were sacrificed by rapid carotid exsanguinations’ under ether anesthesia. Lumbar (L-4) ventral and dorsal roots were excised with laminectomy and immediately placed in a modified chilly Krebs solution saturated with 95% 02, and 5% CO2. To evaluate effect of 4-AP on the roots, CAP’s were recorded in a modified sucrose gap chamber in vitro. All experiments were performed at 20-22 oC. Results: The total duration of CAP obtained from the ventral root was prolonged by 4-AP and the return to baseline was delayed. The duration of CAP of the dorsal root more broadened than ventral roots at least two fold. The CAP of the dorsal roots developed a distinct hump when return to baseline. This phenomenon was not observed in ventral roots. The latency of ventral and dorsal root were 256 ± 24 and 508 ± 69 µs, conduction velocity 20.4 ± 2.4 and 10.8 ± 1.4 m/s, respectively. Conclusion: In this study we showed that 4-AP has entirely different effects on rat motor and sensory axons. The differential effect of 4-AP on motor and sensory fibers may be due to differences in ratio of myelinated-unmyelinated axons and its diameters. In addition there may be differences node or paranode’s potassiumsodium channels diversity in ventral and dorsal roots

Anahtar Kelimeler

• Ventral-Dorsal Root
• Action Potential
• 4-Aminophyridine
• Sucrose-gap

Kaynakça

1. Guyton and Hall. Medical Physiology, 9. ed. 1996: 57-72, 565-580.
2. William F. Ganong. Tıbbi Fizyoloji, 17.baskı, I.cilt, 1996: 61-75.
3. Junquiera LC, Carneiro J. Basic Histology: Text and atlas. 10. ed, New York, Lange Mc Graw Hill, 2003.
4. Ross MH, Pawlina W. Histology: A text and atlas. Baltimore, Philadelphia, 5. ed, Lipincott Williams&Wilkins, 2006.
5. Steven S. Scherer. Myelination: some receptors required. The Journal of Cell Biology, 2002;156(1):13–15.
6. H. Schmalbruch. Fiber Composition of the Rat Sciatic Nerve. The Anatomical Record 1986;215:71-81.
7. Mustafa GÜVEN, İbrahim KAHRAMAN, Filiz KOÇ, Hacer BOZDEMİR, Yakup SARICA, İsmail GÜNAY. The Effects of Oxcarbazepine on 4-Aminopyridine-Induced Afterpotentials on Isolated Rat Sural Nerves. Journal of Neurological Sciences [Turk] 2010;27:(2): 139-149.
8. Guven M, Kahraman I, Güneş Y, Gunay I.: Effect of Tramadol on peripheral nerves: An in-vitro electrophysiological study on the sural and tibial nerves of the rat. Journal of Medical Science (Türkiye Klinikleri). 2011;31(1).

9. Waxman SG, Ritche JM: Molecular dissection of the myelinated axon. Ann Neurol 1993:33:121-136. 10. Rizzo MA, Kocsis JD, Waxman SG. Slow sodium conductances of dorsal root ganglion neurons: intraneuronal homogeneity and interneuronal heterogeneity. J Neurophysiol. 1994 Dec;72(6):2796-815. 11. Honmou, O., Utzschneider, D.A., Rizzo, M.A., Bowe, C.M., Waxman, S.G., Kocsis, J.D.,. Delayed depolarization and slow sodium currents in cutaneous afferents. J. Neurophysiol. 1994;71:1627–1637.
10. Nonaka T, Honmou O, Sakai J, Hashi K, Kocsis JD. Excitability changes of dorsal root axons following nerve injury: implications for injury-induced changes in axonal Na+ channels. Brain Research. 2000;859:280-285.
11. Kocsis JD and Waxman SG. Ionic channel organization of normal and regenerating mammalian axons. Progress in Brain Research. Vol. 71. 1987.
12. Mert T, Güneş Y, Güven M, Gunay I and Göçmen C. Differential effects of lidocaine and tramadol on modified nerve impulse by 4-aminophyridine in rat. Pharmacology, 2003;69(2): 68-73.
13. Kocsis JD and Waxman SG. Membrane Organization and Myelin Remodelling in regenerating Axons. Advances in Neurology, Vol 47: Functional Recovery in Neurological Disease. 1988.
14. Sakai J, Honmou O, Kocsis JD, Hashi K. The delayed depolarization in rat cutaneous afferent axons is reduced following nerve transection and ligation, but not crush: implications for injury-induced axonal Na+ channel reorganization. Muscle and Nerve 1998;21(8):1040-7
15. Hildebrand C, Kocsis JD, Berglund S, Waxman SG. Myelin sheath remodelling in regenerated rat sciatic nerve. Brain Research. 1985;358:163-170.
16. Hildebrand C, Bowe CM, Remahl IN. Myelination and myelin sheath remodelling in normal and pathological PNS nerve fibers. Progress in Neurobiology. 1994; 43:85-141.
17. Fehlings MG, Nashmi R. Changes in pharmacological sensitivity of the spinal cord to potassium channel blockers following acute spinal cord injury. Brain Research. 1996;736:135-145.
18. Stampfli R.: A new method for measuring potentials with external electrodes. Experienta, 1954;10:508-509. 21. Beth Dawson, Robert G. Trapp. Basic & Clinical Biostatistics. April 15, 2001.