위장관 평활근 수축기전과 신경전달의 새로운 개념: Fibroblast-like Cells
Smooth Muscles Contraction in Gastrointestinal Tract and New Concept of Enteric Neurotransmission: Fibroblast-like Cells
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위장관 평활근의 수축은 서파에 의해 발생하며, 서파는 ICC에서 발생한다. RYR3 수용체의 점화로 시작된 ICC 세포내 Ca2+ 농도증가는 세포막의 Ca2+-sensitive chloride channels을 활성화하여 STIC을 유발하고 합쳐져 STD를 만들고, gap junction을 통하여 위장관 평활근으로 전달된다. 평활근 세포막으로 전달된 신호에 의한 VOD의 활성화로, 평활근 세포내 Ca2+이 증가되고, calmodulin과 결합하여 결합체를 형성하며, 활성화된 MLC kinase에 의한 미오신 경사슬 형성은 평활근 수축을 유발한다. 위장관의 신경은 억제신경으로, 평활근 세포막의 수용체와 연계된 G 단백을 통한 반응으로 수축의 강약과 기간에 영향을 미치고, ICC 세포막의 InsP2, cGMP 경로를 통하여 ICC pacemaking의 빈도를 조절하는 역할을 한다. FLCs은 PDGFRα+의 새로 밝혀지고 있는 간질세포로, 형태학적으로 신경얼기와 평활근과의 gap junction을 가지고 있으며, SK3로 알려진 Ca2+ activated K+ channel을 다수 보유하고 있어, 내장신경말단에서 평활근으로의 신호전달체계를 밝히는 중요한 열쇠일 것이다.
Abstract
This review provides information regarding an enteric neurotransmission from enteric nerve terminals to smooth muscles. In the gastrointestinal tract, phasic contractions are caused by electrical activity termed slow waves. Slow waves are generated and actively propagated by interstitial cells of Cajal (ICC). The initiation of pacemaker activity in the ICC is caused by release of Ca2+ from inositol 1, 4, 5-trisphosphate (IP3) receptor-operated stores, and the development of unitary currents. Summation of unitary currents causes depolarization and activation of a dihydropyridine-resistant Ca2+ conductance that entrains pacemaker activity in a network of ICC, resulting in the active propagation of slow waves. Slow wave frequency is regulated by a variety of physiological agonists and conditions, and shifts in pacemaker dominance can occur in response to both neural and non-neural inputs. Fibroblast-like cells (FLCs) are also closely associated with nerve varicosities and are labelled robustly with antibodies for platelet-derived growth factor receptor α (PDGFRα), and expression of this receptor may be a powerful new means of isolating and evaluating the function of FLCs and the possible contribution of these cells in disease. PDGFRα+ cells share similar anatomical distributions, and FLCs in colonic smooth muscle functionally express small conductance Ca2+-activated K+ channel (SK3). These findings are important to understand purinergic post-junctional responses. (Korean J Med 2011;81:315-321)
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