The effects of age and disease on gap junctions and ion channels and their potential value to the treatment of erectile dysfunction
The effects of age and disease on gap junctions and ion channels and their potential value to the treatment of erectile dysfunction
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DOI：
10.1016/s0094-0143(05)70133-6
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发表时间：
2001-05-01
影响因子：
2.4
通讯作者：
Christ, GJ
中科院分区：
文献类型：
--
作者：
Melman, A;Christ, GJ
体平滑肌张力的启动、维持和调节严重依赖于激动剂诱导的细胞内钙水平和动员以及跨膜钙通量的变化。在细胞水平上对肌细胞兴奋性和收缩性的瞬时控制与膜电位密不可分，而膜电位又通过四种已知的皮质平滑肌钾离子通道之一的钾离子流出来调节。随后通过细胞内第二信使分子（即，IP 3，cAMP，cGMP）和离子（即，K+和Ca ~（2+））通过间隙连接通道进行细胞间通讯。了解这些相互连接的细胞（非连接离子通道[例如，maxi-K]）和组织（间隙连接通道[例如，连接蛋白43]）系统对调节勃起能力的作用，为公布hSlo离子通道基因治疗用于使老年大鼠和糖尿病大鼠的勃起状态正常化的成功临床前试验提供了科学依据。
Initiation, maintenance, and modulation of corporal smooth muscle tone are critically dependent upon agonist-induced changes in intracellular calcium levels and mobilization as well as transmembrane calcium flux. The transient control of myocyte excitability and contractility at the cellular level is inextricably linked to membrane potenial, which, in turn, is modulated by potassium ion efflux through one of the four known corporeal smooth muscle potassium ion channels. Corporal tissue responses are subsequently coordinated by means of the movement of intracellular second messenger molecules (i.e., IP3, cAMP, cGMP) and ions (i.e., K+ and Ca2+) among the corporal myocytes by means of intercellular communication through gap junction channels. Knowledge of the critical contribution of these interlinking cellular (nonjunctional ion channels [e.g, maxi-K]) and tissue (gap junction channels [e.g., connexin 43]) systems to the modulation of erectile capacity has provided the scientific rationale for the promulgation of the successful preclinical testing of hSlo ion channel gene therapy for the normalization of erectile status in both aged and diabetic rats.