Molecular Mechanism of General Anesthesia

Abstract

Despite the widespread changes induced by general anesthetic agents, their exact effect sites are not clearly defined in the central nervous system (CNS). Recent molecular studies have pointed out specific sites in CNS on which anesthetic drugs show their effects. Hypnosis, amnesia, sedation are mediated by different receptors, neurotransmitters and neuronal pathways in the CNS. Protein base theory of anesthesia, which focuses on ion channels, took the place of lipid-based theory in the 1980’s. There are two types of receptors, which are known to be responsible for the general anes-thetic action: neurotransmitter receptors and ion channels. Back-ground channels are also described as targets for anesthetic ac-tion. Enhancement and block of TWIK Related K+ channels (TREK), TWIK related arachidonic acid activated K+ channel (TRAAK), and TWIK related acid-sensitive K+ channels (TASK) channels have been reported at low concentrations of volatile anesthetic agents. Two-pore-domain potassium channels are protein complexes em-bedded in cell membranes. They selectively allow potassium ions to pass through the cellular membrane. These channels are also ca-pable of changing the membrane potential by means of neuronal excitability, neurotransmitters and hormone secretion. Of those channels, TASK-1 and TREK-1 are activated by volatile anesthetic agents. In this article, receptors responsible for anesthesia in CNS and their mechanism of action will be reviewed.

Keywords

• General anesthesia
• Molecular pharmacology
• Consciousness

Genel Anesteziklerin Moleküler Mekanizması

Abstract

Genel anestezik ajanlar, nörotransmitterleri modüle ederek santral sinir sisteminde yaygın nöronal değişime neden olmaktadır. Yeni yapılan moleküler araştırmalarda anestezik ajanların etki ettiği spesifik alanlar üzerinde durulmaktadır. Hipnoz, amnezi, sedasyon santral sinir sisteminde farklı reseptör, nörotransmitter ve nöronal yolaklar aracılığıyla sağlanır. 1980'lerin başında yapılan çalışmalar sonrasında, iyon kanallarına odaklanan protein temelli anestezi te-orisi, lipid temelli anestezi teorisinin yerini almıştır. Protein temelli teoriye göre, genel anestezik etkiden sorumlu iki tip reseptör mev-cuttur; nörotransmitter reseptörler ve iyon kanalları. “Background” iyon kanalları da anestezik etki için yeni tanımlanmış hedef resep-törlerdir. İki porlu (two-pore-domain) potasyum kanallarından TWIK ilişkili K+ kanalı (TREK), TWIK ilişkili araşidonik asitle aktive K+kanalı (TRAAK), TWIK ilişkili asit duyarlı K+ kanalları (TASK) tipteki kanalların volatil ajanların düşük konsantrasyonunda güçlendiği ya da bloke olduğu bildirilmiştir. İki porlu potasyum kanalları, biyolo-jik membranlarda bulunan protein kompleksleridir. İki porlu potas-yum kanalları, potasyum iyonları için özeldir ve potasyumun hücre membranından geçmesine izin verirler. İki porlu potasyum kanal-ları, nöronal uyarılma, nörotransmitter ve hormon salınımı yoluyla, membran potansiyelindeki değişikliklerden de sorumludurlar. İki porlu potasyum kanalların TASK-1 ve TREK-1 alt tipleri volatil anes-tezik ajanlarla (örneğin, izofluran, kloroform, dietil eter) uyarılır. Bu makalede santral sinir sisteminde bulunan ve genel anesteziklerin etkisinden sorumlu reseptörler ve bunların etki mekanizmaları gözden geçirilecektir.

Keywords

• Genel Anestezi
• Moleküler Farmakoloji
• Bilinç

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